| 1. |
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| 2. |
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| 3. |
- Fergedal, May, et al.
(författare)
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Differences in CD14 and alpha-naphthyl acetate esterase positivity and relation to prognosis in AML
- 1998
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Ingår i: Leukemia Research. - Oxford, United Kingdom : Elsevier. - 0145-2126 .- 1873-5835. ; 22:1, s. 25-30
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Tidskriftsartikel (refereegranskat)abstract
- Alpha-naphthyl acetate esterase (ANAE) and CD14 expression, used for determination of monocytic cells, were compared and related to prognosis in 65 AML patients. Bone marrow aspiration material from AML patients has been used for the cytochemistry as well as flow cytometry. All non-erythroid cells have been included in the evaluation in both methods. 17/65 cases showed at least 15% difference between the proportion CD14 and ANAE positive cells. Cases with 20% or more CD14 positivity had poorer prognosis. For FAB classes M0-M3, presence of 10% or more CD14 was negative for overall survival (P = 0.01). ANAE did not show significant prognostic influence.
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| 4. |
- Gruber, A, et al.
(författare)
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A phase I/II study of the MDR modulator Valspodar (PSC 833) combined with daunorubicin and cytarabine in patients with relapsed and primary refractory acute myeloid leukemia
- 2003
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Ingår i: Leukemia Research. - 0145-2126 .- 1873-5835. ; 27, s. 323-
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Tidskriftsartikel (refereegranskat)abstract
- The cyclosporine analog Valspodar (PSC 833, Novartis Pharma) is a strong inhibitor of the mdr1 gene product p-glycoprotein (pgp). A phase I/II study was conducted in order to evaluate if addition of Valspodar to treatment with daunorubicin and cytarabine, given to patients with primary refractory or relapsed acute myeloid leukemia, could increase the complete remission rate. Fifty-three patients were treated in cohorts of three to six patients. Twelve patients reached a complete remission in bone marrow, five of whom also normalized their peripheral blood values. Three patients experienced treatment-related deaths from pneumonia, liver failure and cerebral hemorrhage, respectively. It is concluded that Valspodar 10mg/kg per 24h in combination with daunorubicin 45mg/m2 for 3 days and cytarabine 1g/m2 twice daily for 4 days is tolerable in this heavily pre-treated group of patients. Due to the moderate treatment results, the phase II part of the study was ended prematurely. The modulation of only pgp did not give an obvious improvement of the treatment results in this group of patients. ⌐ 2002 Elsevier Science Ltd. All rights reserved.
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| 5. |
- Knaust, Eva, 1944-, et al.
(författare)
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Different effects of metabolic inhibitors and cyclosporin A on daunorubicin transport in leukemia cells from patients with AML
- 2003
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Ingår i: Leukemia Research. - 0145-2126 .- 1873-5835. ; 27:2, s. 183-191
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to determine the role of transport proteins in daunorubicin (Dnr) accumulation and efflux in leukemia cells from 36 patients with acute myeloid leukemia (AML). Mononuclear cells were isolated and incubated with 1 μM Dnr with/without addition of 3 μM cyclosporin A (CyA) or metabolic inhibitors (MI). Cellular Dnr concentration in leukemia blast cells was measured with flow cytometry. After washing and reincubation of the cells in drug-free medium, Dnr efflux was followed with/without addition of CyA or MI. Levels of mRNA expression for mdr1, multidrug resistance associated protein (mrp) and lung resistance protein (lrp) were determined with reverse transcriptase-polymerase chain reaction (RT-PCR). MI enhanced cellular Dnr accumulation to a higher extent than CyA whereas CyA reduced Dnr efflux more efficiently than MI (P<0.001). There was a significant difference in Dnr accumulation between samples with low and high mdr1 mRNA levels but only in the presence of MI or CyA. Our results imply that other factors than P-glycoprotein (Pgp) are of major importance for in vitro Dnr accumulation in AML blasts and that the role of Pgp as a drug efflux pump is not conclusive.
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| 6. |
- Uggla, Bertil, 1962-, et al.
(författare)
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Expression of topoisomerase IIalpha in the G0/G1 cell cycle phase of fresh leukemic cells
- 2001
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Ingår i: Leukemia Research. - Oxford, United Kingdom : Elsevier. - 0145-2126 .- 1873-5835. ; 25:11, s. 961-966
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Tidskriftsartikel (refereegranskat)abstract
- Topoisomerase IIalpha (topoII alpha) is the target enzyme for several antineoplastic drugs. Correlation between low expression of topo IIalpha and drug resistance has been shown in vitro, but there is limited evidence of a correlation to initial response to treatment or to overall prognosis. Normal cells express topo IIalpha in S/G2/M phase of the cell cycle but not in G0/G1 phase. However, some data suggest that topo IIalpha could be expressed in G0/G1 phase in malignant cells. We have investigated the expression of topo IIalpha in leukemic cells from 25 patients with acute leukemia by flow cytometry, separating cells of different cell cycle phases. We demonstrated that 9/25 samples showed >50% positive cells in G0/G1, and another five samples showed >20%. This finding could possibly provide an explanation to previous difficulties in correlating topo IIalpha expression with clinical outcome. Six of eight patients, where >20% of the cells in G0/G1 were positive for topo IIalpha, entered CR, compared to one of five patients with <20% topo IIalpha positive cells in G0/G1. We suggest that topo IIalpha expression in G0/G1 in leukemic cells may be of predictive value for clinical response to cytostatic drugs.
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| 7. |
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| 8. |
- Andersen, Christen Lykkegaard, et al.
(författare)
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Circulating YKL-40 in patients with essential thrombocythemia and polycythemia vera treated with the novel histone deacetylase inhibitor vorinostat
- 2014
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Ingår i: Leukemia Research. - : Elsevier. - 0145-2126 .- 1873-5835. ; 38:7, s. 816-821
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Tidskriftsartikel (refereegranskat)abstract
- YKL-40 regulates vascular endothelial growth factors and induces tumor proliferation. We investigated YKL-40 before and after treatment with vorinostat in 31 polycythemia vera (PV) and 16 essential thrombocythemia (ET) patients. Baseline PV patient levels were 2 times higher than in healthy controls (P<0.0001) and 1.7 times higher than in ET (P = 0.02). A significant correlation between YKL-40 at baseline and neutrophils, CRP, LDH, JAK2V617F and platelets in PV patients was observed, as well as a significantly greater reduction of YKL-40 levels in PV patients responding to therapy. YKL-40 might be a novel marker of disease burden and progression in myeloproliferative neoplasms.
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| 9. |
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| 10. |
- Besses, Carlos, et al.
(författare)
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Cytoreductive treatment patterns for essential thrombocythemia in Europe. Analysis of 3643 patients in the EXELS study
- 2013
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Ingår i: Leukemia Research. - : Elsevier BV. - 0145-2126 .- 1873-5835. ; 37:2, s. 162-168
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Tidskriftsartikel (refereegranskat)abstract
- EXELS is an ongoing phase IV non-interventional study; 3643 high-risk patients with essential thrombocythemia (ET) were recruited across 13 European countries. We report patient characteristics and cytoreductive treatment patterns of ET across Europe. Hydroxycarbamide (HC; 64.3%) and anagrelide (22.0%) were the two main cytoreductive treatments prescribed. The proportions of patients taking either HC or anagrelide varied across countries, as did the number of patients receiving anti-aggregatory therapy in addition to cytoreductive treatment. This real-world evidence demonstrates that, generally, treatment patterns of ET across Europe adhere to expert recommendations, with some notable variations between countries.
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| 11. |
- Birgegård, Gunnar, 1944-, et al.
(författare)
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Leukemic transformation and second cancers in 3649 patients with high-risk essential thrombocythemia in the EXELS study
- 2018
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Ingår i: Leukemia Research. - : Elsevier BV. - 0145-2126 .- 1873-5835. ; 74, s. 105-109
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Tidskriftsartikel (refereegranskat)abstract
- EXELS, a post-marketing observational study, is the largest prospective study of high-risk essential thrombocythemia (ET) patients, with an observation time of 5 years. EXELS found higher event rates of acute leukemia transformation in patients treated with hydroxycarbamide (HC). In the current analysis, we report age-adjusted rates of malignant transformation from 3460 EXELS patients exposed to HC, anagrelide (ANA), or both. At registration, 481 patients had ANA treatment without HC exposure, 2305 had HC without ANA exposure, and 674 had been exposed to both. Standard incidence ratios (SIRs) were calculated using data from the Cancer Incidence in Five Continents database to account for differences in age-, gender-, and country-specific background rates. SIRs for acute myelogenous leukemia (AML) were high in ET patients. SIRs for AML were high in HC-treated patients, but AML was rare in ANA-treated patients; no cases of AML were found in patients only treated with ANA. No statistically significant difference was seen between SIRs for ANA and HC treatment for AML or skin cancer. SIRs for other cancers were similar in the HC and ANA groups and close to 1, indicating little difference in risk. Although statistically inconclusive, this study strengthens concerns regarding possible leukemogenic risk with HC treatment. (NCT00202644)
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| 12. |
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| 13. |
- Björk, Jonas, et al.
(författare)
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Smoking as a risk factor for myelodysplastic syndromes and acute myeloid leukemia and its relation to cytogenetic findings: A case-control study.
- 2009
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Ingår i: Leukemia Research: A Forum for Studies on Leukemia and Normal Hemopoiesis. - : Elsevier BV. - 1873-5835. ; Nov 17, s. 788-791
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Tidskriftsartikel (refereegranskat)abstract
- In this case-control study, interview data on smoking habits were available for 179 de novo cases (116 with cytogenetic data) of acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). Smoking habits were compared with a pooled set of population controls and hospital controls (diagnosed with malignant melanoma). Each pack-year of smoking increased the risk of MDS with 1.3% (95% CI 0.1-2.6%), corresponding to an estimated excess risk of 71% (95% CI 3-180%) for 40 pack-years. Associations between smoking and the specific aberrations -5/5q-, -7/7q-, and +8 in AML and MDS were indicated but the estimates were imprecise.
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| 14. |
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| 15. |
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| 16. |
- Daskalakis, M., et al.
(författare)
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Trisomy 19 as the sole chromosomal abnormality in proliferative chronic myelomonocytic leukemia
- 2006
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Ingår i: Leukemia Research: A Forum for Studies on Leukemia and Normal Hemopoiesis. - : Elsevier BV. - 1873-5835. ; 30:8, s. 1043-1047
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Tidskriftsartikel (refereegranskat)abstract
- Distinct morphologic and clinical features associated with specific chromosomal abnormalities have been described in subgroups of myelodysplastic syndromes (MDS), which often are losses or gains and only rarely translocations. Among 103 consecutive MDS patients diagnosed and karyotyped at the Albert-Ludwigs University of Freiburg (ALU) between 1993 and 1999, two chronic myelomonocytic leukemias (CMMoL) displayed trisomy 19 (+19) as the sole chromosomal abnormality. Three further CMMoL cases with +19 as the single abnormality, two of which previously reported, were collected from other centers. Four of the five patients presented with leukocytosis and splenomegaly, and an increased number of ringed sideroblasts was observed in two cases. Treatment was low-dose Decitabine (cases 1 and 2), oral steroids (case 3), hydroxyurea (case 4), and daunorubicin/Ara-C (case 5). Transformation to acute myeloid leukemias (AML) occurred in three/five patients (cases 1, 2, and 4) 26, 12, and 22 months after diagnosis of CMMoL, respectively. We conclude that +19 as the sole anomaly is a rare but recurrent change in CMMoL, in particular of the proliferative type. It is at present unclear which gene(s) located on chromosome 19 might have a functional role for the development of this phenotype. (c) 2006 Elsevier Ltd. All rights reserved.
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| 17. |
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| 18. |
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| 19. |
- Ek, Sara, et al.
(författare)
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Transcriptional profiling and assessment of cell lines as in vitro models for mantle cell lymphoma
- 2005
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Ingår i: Leukemia Research: A Forum for Studies on Leukemia and Normal Hemopoiesis. - : Elsevier BV. - 1873-5835. ; 29:2, s. 205-213
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Tidskriftsartikel (refereegranskat)abstract
- Mantle cell lymphoma (MCL) is an aggressive malignancy and new treatment modalities must be established to increase patient survival time. In the search for new therapeutic targets, reliable and well-characterised in vitro models are essential. In this study, we have characterised three MCL cell lines (SP53, Granta 519 and NCEB1) in comparison with primary tumors front MCL, follicular lymphomas (FL), a(.)FL cell line(RL), a Burkitt lymphoma cell line (RAJI) and five different B cell populations from healthy individuals. Expression profiling was used to determine the relative expression of >12000 transcripts in these samples, and flow cytometry analysis was performed to establish a phenotypic signature for each of the cell lines. In addition, the cell lines were sequenced, and the frequency of somatic Mutations and immunoglobulin (Ig) variable heavy chain (V-H) Usage were determined. We show by hierarchical clustering that the cell lines retain a genetic signature similar to primary MCL, which readily separated the MCL samples front the other lymphoma cell lines and the FL tumours. Furthermore, the MCL cell lines showed differences in the frequency of V-H somatic mutations (0-2.1%). The increased number of mutations in NCEB1, compared to the other MCL cell lines, was in agreement with a decreased expression of CD31, CD44, CXCR5, CCR7 and CCR6. Taken together, our data show that the cell lines are clearly derived from MCL tumours and expressed similar genetic and phenotypic signatures compared to primary tumours, which confirmed their usefulness as in vitro models. (C) 2004 Elsevier Ltd. All rights reserved.
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| 20. |
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| 21. |
- Eriksson, Anna, 1977-, et al.
(författare)
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Towards repositioning of quinacrine for treatment of acute myeloid leukemia - Promising synergies and in vivo effects.
- 2017
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Ingår i: Leukemia Research. - : Elsevier BV. - 0145-2126 .- 1873-5835. ; 63, s. 41-46
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Tidskriftsartikel (refereegranskat)abstract
- We previously reported that the anti-malarial drug quinacrine has potential to be repositioned for treatment of acute myeloid leukemia (AML). As a next step towards clinical use, we assessed the efficacy of quinacrine in an AML-PS mouse model and investigated possible synergistic effects when combining quinacrine with nine other antileukemic compounds in two AML cell lines. Furthermore, we explored the in vivo activity of quinacrine in combination with the widely used AML agent cytarabine. The in vivo use of quinacrine (100mg/kg three times per week for two consecutive weeks) significantly suppressed circulating blast cells at days 30/31 and increased the median survival time (MST). The in vitro drug combination analysis yielded promising synergistic interactions when combining quinacrine with cytarabine, azacitidine and geldanamycin. Finally, combining quinacrine with cytarabine in vivo showed a significant decrease in circulating leukemic blast cells and increased MST compared to the effect of either drug used alone, thus supporting the findings from the in vitro combination experiments. Taken together, the repositioning potential of quinacrine for treatment of AML is reinforced by demonstrating significant in vivo activity and promising synergies when quinacrine is combined with different agents, including cytarabine, the hypomethylating agent azacitidine and HSP-90 inhibitor geldanamycin.
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| 22. |
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| 23. |
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| 24. |
- Flordal Thelander, Emma, et al.
(författare)
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Detailed assessment of copy number alterations revealing homozygous deletions in 1p and 13q in mantle cell lymphoma
- 2007
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Ingår i: Leukemia Research. - : Elsevier BV. - 0145-2126 .- 1873-5835. ; 31:9, s. 1219-1230
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Tidskriftsartikel (refereegranskat)abstract
- Mantle cell lymphoma (MCL) is characterized by over-expression of cyclin Dl as a result of the characteristic t(11;14)(q13;q32). However, this translocation alone has proven not to be sufficient for lymphomagenesis, suggesting the involvement of additional alterations. We have characterized 35 cases of MCL by array comparative genomic hybridization with an average resolution of 0.97Mb distributed over the complete human genome. The most common alterations were losses in 1p13.2–p31.1, 6q16.2–q27, 8p21.3, 9p13.2–p24.3, 9q13–q31.3, 11q14.3–q23.3, 13q14.13–q21.31, 13q33.1–q34, and 22q11.23–q13.33 and gains involving 3q21.2–q29, 7p12.1–p22.3, 8q24.13–q24.23, and 18q21.33–q22.3. Four homozygous deletions were identified in totally three patients; two overlapping at 1p32.3, and two adjacent at 13q32.3. The homozygous deletions at 1p32.3 cover the CDKN2C locus (coding for p18), while the region at 13q32.3 does not encompass any known tumor suppressor genes. A gain in 3q was significantly associated with shorter survival (P=0.047).
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| 25. |
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| 26. |
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| 27. |
- Hagberg, Anette, et al.
(författare)
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Gene expression analysis identifies a genetic signature potentially associated with response to alpha-IFN in chronic phase CML patients
- 2007
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Ingår i: Leukemia Research. - : Elsevier BV. - 0145-2126 .- 1873-5835. ; 31:7, s. 931-938
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Tidskriftsartikel (refereegranskat)abstract
- Microarray-based gene expression analysis was performed on diagnostic chronic phase CML patient samples prior to interferon treatment. Fifteen patient samples corresponding to six cytogenetic responders and nine non-responders were included. Genes differentially expressed between responder and non-responder patients were listed and a subsequent leave-one-out cross validation (LOOV) procedure showed that the top 20 genes allowed the highest prediction accuracy. The relevant genes were quantified by real-time PCR that supported the microarray results. We conclude that it might be possible to use gene expression analysis to predict future response to interferon in CML diagnostic samples.
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| 28. |
- Holm, Caroline, et al.
(författare)
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Cyclin A1 expression and associations with disease characteristics in childhood acute lymphoblastic leukemia
- 2006
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Ingår i: Leukemia Research. - : Elsevier. - 0145-2126 .- 1873-5835. ; 30:3, s. 254-261
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Tidskriftsartikel (refereegranskat)abstract
- A critical cell cycle regulatory protein, cyclin A1, has been implicated in the development of acute myeloid leukemia (AML). Here, we have examined the expression and clinical significance of cyclin A1 in childhood acute lymphoblastic leukemia (ALL). Cyclin A1 was highly expressed in lymphoblastic leukemic cell lines and in 22 of 30 ALL patients (73%). Cyclin A1 expression correlated with patient age (P=0.006), but not with cytogenetic abnormalities. Patients with high levels of cyclin A1 had poorer event-free survival (57.9%) compared to patients with lower levels (75%).
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| 29. |
- Jansson, Johan, et al.
(författare)
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Acute lymphoblastic leukemia cells that survive combination chemotherapy in vivo remain sensitive to allogeneic immune effects
- 2011
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Ingår i: Leukemia Research. - : Elsevier BV. - 0145-2126 .- 1873-5835. ; 35:6, s. 800-807
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Tidskriftsartikel (refereegranskat)abstract
- Allogeneic hematopoietic stem cell transplantation is often performed for patients with acute lymphoblastic leukemia (ALL) whose disease has relapsed after chemotherapy treatment. However, graft versus leukemia (GVL) effects in ALL are generally weak and the mechanisms of this weakness are unknown. These studies tested the hypothesis that ALL cells that have survived conventional chemotherapy in vivo acquire relative resistance to the allogeneic GVL effect. C57BL/6 mice were injected with murine pre-B ALL lines driven by human mutations and then were treated with combination chemotherapy. ALL cells surviving therapy were analysed in vitro and in vivo for acquisition of resistance to chemotherapy, radiation, cytolytic T cells, NK cells, LAK cells and cytokines. In vivo drug treatment did lead to leukemia population with more rapid proliferation and also decreased sensitivity to vincristine, doxorubicin and radiation. However, drug treatment did not produce ALL populations that were less sensitive to GVL effects in vitro or in vivo.
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| 30. |
- Kaderi, Mohd Arifin, et al.
(författare)
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Lack of association between the MDM2 promoter polymorphism SNP309 and clinical outcome in chronic lymphocytic leukemia
- 2010
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Ingår i: Leukemia Research. - : Elsevier BV. - 0145-2126 .- 1873-5835. ; 34:3, s. 335-339
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Tidskriftsartikel (refereegranskat)abstract
- The 309T>G polymorphism in the promoter region of the MDM2gene, known as SNP309, has recently been suggested as an unfavorable prognostic marker in chronic lymphocytic leukemia (CLL) although this has been questioned. To investigate this further, we analyzed the MDM2 SNP309 genotypes in 418 CLL patients and correlated the results with established CLL prognostic factors, time to treatment and overall survival. In this Swedish cohort, no association existed between any particular MDM2 SNP309 genotype, overall survival and time to treatment. Furthermore, no correlation was shown between the MDM2 SNP309 genotypes and Binet stage, IGHV mutational status and recurrent genomic aberrations. In summary, this study argues against the use of the MDM2 SNP309 as a prognostic marker in CLL.
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| 31. |
- Kaderi, Mohd Arifin, et al.
(författare)
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The GNAS1 T393C polymorphism and lack of clinical prognostic value in chronic lymphocytic leukemia
- 2008
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Ingår i: Leukemia Research. - : Elsevier BV. - 0145-2126 .- 1873-5835. ; 32:6, s. 984-987
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Tidskriftsartikel (refereegranskat)abstract
- Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease with no known single predisposing genetic factor shown in all cases. Recently, a single nucleotide polymorphism (SNP) T393C in the GNAS1 gene has been reported to have a clinical impact on CLL progression and overall survival. In order to further investigate the T393C SNP in CLL, we have genotyped 279 CLL cases and correlated the genotypes to clinical outcome and other known prognostic factors such as the immunoglobulin heavy chain variable (IGHV) gene mutation status and CD38 expression. In the present study, no difference in overall survival or time to treatment was observed in the CLL patients with the different genotypes in contrast to the previous report. Furthermore, no correlation was observed with the T393C genotypes and IGHV mutational status, Binet stage or CD38 in this cohort. In summary, our data does not support the use of the T393C GNAS SNP as a clinical prognostic factor in CLL.
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| 32. |
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| 33. |
- Larfors, Gunnar, et al.
(författare)
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MDS-Comorbidity Index using register data has prognostic impact in Swedish MDS patients
- 2023
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Ingår i: Leukemia Research. - : Elsevier. - 0145-2126 .- 1873-5835. ; 134
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Tidskriftsartikel (refereegranskat)abstract
- Comorbidities influence the mortality in patients with myelodysplastic syndromes, and a growing body of evidence suggest that comorbidity history should be used in addition to established prognostic indices. A comorbidity index specific for MDS, the MDS-CI, was introduced a decade ago. In this study we aim to construct an MDS-CI version based on diagnoses from register data only, to expand its use beyond the clinical setting to retrospective and register based studies. We further test this version on a Swedish population-based MDS cohort of 2947 patients, and compare its prognostic accuracy to that of Charlson Comorbidity Index. Our register based MDS-CI divided patients into three risk groups of similar proportions as have been published for the original MDS-CI. Compared to low risk patients, intermediate and high risk patients had 50 % and 70 % higher mortality, respectively. The prognostic value of MDS-CI was equal to that of Charlson comorbidity index. Adding MDS-CI to the established prognostic factors IPSS-R and age increased the prognostic accuracy. In summary, we demonstrate that MDS-CI can be adequately estimated from diagnoses recorded in registers only, and that it is a useful tool in any future study on myelodysplastic syndromes with a need to adjust for comorbidities.
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| 34. |
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| 35. |
- Li, Aihong, et al.
(författare)
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Detailed clonality analysis of relapsing precursor B acute lymphoblastic leukemia : implications for minimal residual disease detection.
- 2001
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Ingår i: Leukemia Research. - 0145-2126 .- 1873-5835. ; 25:12, s. 1033-45
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Tidskriftsartikel (refereegranskat)abstract
- Genetic instability has important implications for detection of minimal residual disease (MRD) when the target is a clonal genetic marker revealed at diagnosis. A successful MRD detection approach requires a stable marker and for lymphoid leukemias clonal rearrangements of immunoglobulin (Ig) and T cell receptor (TCR) genes are commonly used. In the present study, Ig heavy chain (IgH) and TCR (gamma and delta) genes were studied in 18 consecutive, relapsing precursor-B ALL patients. At least one clonal rearrangement was found in all cases at presentation (IgH 94%, TCRgamma 39% and TCRdelta 28%). An altered rearrangement pattern between diagnosis and relapse was demonstrated in 14 patients (78%). At least one stable molecular target was found in 13 out of 18 cases (72%). Clonal differences between diagnostic and relapse samples were explained by: (1) loss of original rearrangements; (2) V(H) to DJ(H) joining; (3) V(H) gene replacement; (4) appearance of new rearrangements. In two cases with apparently new IgH gene rearrangements at relapse extended sequencing of the diagnostic samples revealed minor clonal rearrangements identical to the relapse clones. Interestingly, one patient displayed instability on both the IgH and TCR gene loci, whereas a stable Igkappa rearrangement was found at presentation and relapse. These data show that clonal diversity is common in precursor-B ALL and strongly suggest that MRD detection should include multiple gene targets to minimize false-negative samples. Even so, five of our 18 relapse cases (28%) lacked stable clonal markers and should have been unsuitable for MRD detection.
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| 36. |
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| 37. |
- Lönnerholm, Gudmar, 1941-, et al.
(författare)
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In vitro cellular drug resistance adds prognostic information to other known risk-factors in childhood acute lymphoblastic leukemia
- 2011
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Ingår i: Leukemia Research. - : Elsevier. - 0145-2126 .- 1873-5835. ; 35:4, s. 472-478
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Tidskriftsartikel (refereegranskat)abstract
- Leukemic cells from 230 children with newly diagnosed B-cell precursor ALL were tested for in vitro drug resistance to a panel of anti-cancer drugs. Minimal residual disease (MRD) was measured by RQ-PCR. During follow-up, 24 relapses occurred in the 159 children with MRD <0.1% day 29. The risk of any relapse was correlated to vincristine and doxorubicin resistance, with a relative risk of 3.7 (95% CI 1.3-10.5; p=0.016) for patients resistant to both drugs. There was a significant correlation also for the subgroup with extra-medullary relapses. Our findings indicate that analysis of drug resistance can add prognostic information to other known risk-factors including MRD.
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| 38. |
- Lönnerholm, Gudmar, et al.
(författare)
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In vitro cellular drug sensitivity at diagnosis is correlated to minimal residual disease at end of induction therapy in childhood acute lymphoblastic leukemia.
- 2009
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Ingår i: Leukemia research. - Oxford : Elsevier BV. - 0145-2126 .- 1873-5835. ; 33:1, s. 46-53
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Tidskriftsartikel (refereegranskat)abstract
- Leukemic cells from 85 children with newly diagnosed precursor B-lineage ALL were tested for in vitro drug sensitivity to a panel of anti-cancer drugs. Minimal residual disease (MRD) was measured by RQ-PCR. There was a significant correlation between MRD day 29 and in vitro sensitivity to prednisolone (p<0.001) and doxorubicin (p=0.017), drugs administered during induction therapy. In patients with t(12;21) (n=20), in vitro sensitivity to doxorubicin was an independent factor for MRD <0.1% (p=0.031; R(2)=0.66). Thus, data show that in vitro drug sensitivity at diagnosis is correlated to cell kill during induction therapy as measured by MRD day 29.
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| 39. |
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| 40. |
- Mansouri, Mahmoud, et al.
(författare)
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Lipoprotein lipase is differentially expressed in prognostic subsets of chronic lymphocytic leukemia but displays invariably low catalytical activity
- 2010
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Ingår i: Leukemia Research. - : Elsevier BV. - 0145-2126 .- 1873-5835. ; 34:3, s. 301-306
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Tidskriftsartikel (refereegranskat)abstract
- Lipoprotein lipase (LPL) expression has been shown to correlate with IGHV mutational status and to predict outcome in chronic lymphocytic leukemia (CLL). We here investigated the prognostic impact of LPL expression in relation to other prognostic markers including IGHV3-21 usage in 140 CLL patients. Additionally, we studied the catalytic activity of LPL in CLL cells. A significant difference in LPL mRNA expression was detected in IGHV unmutated compared to mutated CLL patients (p<0.001). However, the poor-prognostic mutated/stereotyped IGHV3-21 patients did not differ from other mutated CLL cases. Clinical outcome was significantly different in CLL cases with high versus low LPL expression (p<0.001), and LPL expression exceeded mutation status/IGHV3-21 usage as an independent prognostic marker. Finally, LPL protein expression correlated significantly with mRNA expression and was higher in IGHV unmutated versus mutated CLL (p=0.018), although the majority of synthesized protein was catalytically inactive indicating a non-catalytical function in CLL.
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| 41. |
- Masquelier, Michéle, et al.
(författare)
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Cytotoxic effect of a lipophilic alkylating agent after incorporation into low density lipoprotein or emulsions : Studies in human leukemic cells
- 2006
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Ingår i: Leukemia Research. - : Elsevier BV. - 0145-2126 .- 1873-5835. ; 30:2, s. 136-144
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Tidskriftsartikel (refereegranskat)abstract
- The use of low density lipoprotein (LDL) as drug carrier in acute myeloblastic leukemia chemotherapy is attractive due to high LDL uptake by leukemic cells. Lipid-based formulations, such as liposomes or microemulsions are promising alternatives. In the current study, we incorporated N-trifluoroacetyl-adriamycin-14-valerate (AD32), a lipophilic derivative of daunorubicin (DNR), and WB4291, a lipophilic alkylating agent, into LDL or lipid microemulsions and evaluated their cytotoxic activities towards leukemic cell lines using as references DNR and melphalan. The incorporation of AD32 into LDL or emulsion resulted in complexes with poor cytotoxicity. WB4291-LDL and WB4291-emulsion exerted, on the other hand, promising cytotoxic effects towards parental and resistant K562 and HL60 cell lines. © 2005 Elsevier Ltd. All rights reserved.
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| 42. |
- Miftakhova, Regina, et al.
(författare)
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Exploring novel therapeutic options in T-LGL, including epigenetic modulation : a case report
- 2010
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Ingår i: Leukemia Research. - : Elsevier BV. - 0145-2126 .- 1873-5835. ; 34:7, s. e145-e149
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Tidskriftsartikel (refereegranskat)abstract
- T cell large granular lymphocyte leukemia (T-LGL) is a chronic disease covering a wide spectrum of clinical presentations in the border-land between reactive autoimmunity and overt leukemia [1-2]. Most T-LGL patients follow an indolent course, and display a fairly uniform immunophenotype: TCR alfa/beta+, CD3+, CD4-, CD8+, CD56-, CD57+. This disease often causes significant morbidity mediated by anemia and granulocytopenia, considered to occur by mechanism of T cell cytokines. There is no consensus for optimal therapy of T-LGL, but beneficial effects have been reported for a number of agents including cyclosporin, methotrexate, cyclophosphamide and nucleoside analogs [1-2]. However, to the best of our knowledge, there is no experience with some modalities currently in use for closely related disorders. The purpose of the experiments reported in this case report was to evaluate the need for clinical studies on such therapies, including epigenetic modulation and extracorporeal photopheresis.
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| 43. |
- Montano, Giorgia, et al.
(författare)
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The hematopoietic tumor suppressor interferon regulatory factor 8 (IRF8) is upregulated by the antimetabolite cytarabine in leukemic cells involving the zinc finger protein ZNF224, acting as a cofactor of the Wilms' tumor gene 1 (WT1) protein.
- 2016
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Ingår i: Leukemia Research: A Forum for Studies on Leukemia and Normal Hemopoiesis. - : Elsevier BV. - 1873-5835. ; 40:1, s. 60-67
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Tidskriftsartikel (refereegranskat)abstract
- The transcription factor interferon regulatory factor-8 (IRF8) is highly expressed in myeloid progenitors, while most myeloid leukemias show low or absent expression. Loss of IRF8 in mice leads to a myeloproliferative disorder, indicating a tumor-suppressive role of IRF8. The Wilms tumor gene 1 (WT1) protein represses the IRF8-promoter. The zinc finger protein ZNF224 can act as a transcriptional co-factor of WT1 and potentiate the cytotoxic response to the cytostatic drug cytarabine. We hypothesized that cytarabine upregulates IRF8 and that transcriptional control of IRF8 involves WT1 and ZNF224. Treatment of leukemic K562 cells with cytarabine upregulated IRF8 protein and mRNA, which was correlated to increased expression of ZNF224. Knock down of ZNF224 with shRNA suppressed both basal and cytarabine-induced IRF8 expression. While ZNF224 alone did not affect IRF8 promoter activity, ZNF224 partially reversed the suppressive effect of WT1 on the IRF8 promoter, as judged by luciferase reporter experiments. Coprecipitation revealed nuclear binding of WT1 and ZNF224, and by chromatin immunoprecipitation (ChIP) experiments it was demonstrated that WT1 recruits ZNF224 to the IRF8 promoter. We conclude that cytarabine-induced upregulation of the IRF8 in leukemic cells involves increased levels of ZNF224, which can counteract the repressive activity of WT1 on the IRF8-promoter.
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| 44. |
- Norin, Stefan, et al.
(författare)
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Severe infusion-related reactions are uncommon in rituximab-treated CLL patients in clinical practice: Results from a Swedish national observational study
- 2015
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Ingår i: Leukemia Research. - : Elsevier. - 0145-2126 .- 1873-5835. ; 39:1, s. 33-37
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Tidskriftsartikel (refereegranskat)abstract
- There have been concerns about serious infusion-related adverse drug reactions (ADR) with rituximabin chronic lymphocytic leukemia (CLL). We therefore conducted an observational trial in which CLL patients planned for rituximab-containing therapy were eligible. Ninety-six patients from 19 centers were enrolled. The most common regimen was rituximab, fludarabine and cyclophosphamide. Fifty-six patients experienced ADR during rituximab infusion. Reactions greater than= grade 3 occurred in five patients and no cases of tumor lysis syndrome were recorded. Despite a high number of circulating tumor cells few severe ADR were noted. Thus, rituximab containing regimens can be considered safe for CLL patients in general practice.
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| 45. |
- Obad, Susanna, et al.
(författare)
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Expression of the IFN-inducible p53-target gene TRIM22 is down-regulated during erythroid differentiation of human bone marrow.
- 2007
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Ingår i: Leukemia Research: A Forum for Studies on Leukemia and Normal Hemopoiesis. - : Elsevier BV. - 1873-5835. ; 31:7, s. 995-1001
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Tidskriftsartikel (refereegranskat)abstract
- The interferon inducible protein TRIM22 has been identified as a p53 target gene, with possible involvement in proliferation and differentiation of leukaemia cells. Here, the expression levels of TRIM22 during haematopoietic differentiation are characterised. Expression of TRIM22 correlates inversely to differentiation, as TRIM22 is highly expressed in CD34(+) human bone marrow progenitor cells, but declines in mature populations. The erythroid lineage appears as a special case, as TRIM22 expression shows an extreme decrease during late erythroid maturation and is completely undetectable in nucleated erythroid populations in contrast to other lineages. In conclusion, our data Could suggest lineage-specific roles for TRIM22 during haematopoietic differentiation.
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| 46. |
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| 47. |
- Pauly, Frida, et al.
(författare)
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Identification of B-cell lymphoma subsets by plasma protein profiling using recombinant antibody microarrays
- 2014
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Ingår i: Leukemia Research. - : Elsevier BV. - 0145-2126 .- 1873-5835. ; 38:6, s. 682-690
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Tidskriftsartikel (refereegranskat)abstract
- B-cell lymphoma (BCL) heterogeneity represents a key issue, often making the classification and clinical management of these patients challenging. In this pilot study, we outlined the first resolved view of BCL disease heterogeneity on the protein level by deciphering disease-associated plasma biomarkers, specific for chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma, using recombinant antibody microarrays targeting mainly immunoregulatory proteins. The results showed the BCLs to be heterogeneous, and revealed potential novel subgroups of each BCL. In the case of diffuse large B-cell lymphoma, we also indicated a link between the novel subgroups and survival.
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| 48. |
- Radivoyevitch, Tomas, et al.
(författare)
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Risk of acute myeloid leukemia and myelodysplastic syndrome after autotransplants for lymphomas and plasma cell myeloma
- 2018
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Ingår i: Leukemia Research. - : Elsevier BV. - 0145-2126 .- 1873-5835. ; 74, s. 130-136
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Tidskriftsartikel (refereegranskat)abstract
- Background: Exposures to DNA-damaging drugs and ionizing radiations increase risks of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).Methods: 9028 recipients of hematopoietic cell autotransplants (1995-2010) for Hodgkin lymphoma (HL; n=916), non-Hodgkin lymphoma (NHL; n=3546) and plasma cell myeloma (PCM; n=4566), reported to the CIBMTR, were analyzed for risk of subsequent AML or MDS.Results: 335 MDS/ AML cases were diagnosed posttransplant (3.7%). Variables associated with an increased risk for AML or MDS in multivariate analyses were: (1) conditioning with total body radiation versus chemotherapy alone for HL (HR=4.0; 95% confidence interval [1.4, 11.6]) and NHL (HR=2.5 [1.1, 2.5]); (2) >= 3 versus 1 line of chemotherapy for NHL (HR=1.9 [1.3, 2.8]); and (3) subjects with NHL transplanted in 2005-2010 versus 1995-1999 (HR=2.1 [1.5, 3.1]). Using Surveillance, Epidemiology and End Results (SEER) data, we found risks for AML/ MDS in HL, NHL and PCM to be 5-10 times the background rate. In contrast, relative risks were 10-50 for AML and approximately 100 for MDS in the autotransplant cohort.Conclusions: There are substantial risks of AML and MDS after autotransplants for HL, NHL and PCM.
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| 49. |
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| 50. |
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