| 1. |
- Abrahamsson, Jonas, 1954, et al.
(författare)
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Bone marrow fibrosis and radiological changes of the long bones in children with acute megakaryocytic leukaemia.
- 1998
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Ingår i: Acta paediatrica (Oslo, Norway : 1992). - 0803-5253. ; 87:10, s. 1093-6
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Tidskriftsartikel (refereegranskat)abstract
- The diagnosis of acute megakaryocytic leukaemia (AMkL) may be difficult to establish owing to difficulties in obtaining adequate bone marrow aspirates secondary to bone marrow fibrosis. We describe three children without Down's syndrome under 2 y of age with AMkL. Although none of the patients had the non-random t(1;22) (p13;q13) translocation, bone marrow cells from all patients exhibited chromosome abnormalities with complex karyotypes, including trisomy 21 in two cases. All patients had profound bone marrow fibrosis and characteristic lamellar diaphyseal radiological changes of the long bones.
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| 2. |
- Andreasson, Björn, et al.
(författare)
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Plasma erythropoietin concentrations in polycythaemia vera with special reference to myelosuppressive therapy.
- 2000
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Ingår i: Leukemia & lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 37:1-2, s. 189-95
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Tidskriftsartikel (refereegranskat)abstract
- In 80 patients with polycythaemia vera (PV) a total of 108 venous blood samples were obtained and analysed for EDTA-plasma erythropoietin (EPO) concentration. At the time of study 21 of the PV patients were newly diagnosed and had prior to blood sampling neither received phlebotomy treatment nor therapy with myelosuppressive agents; these subjects had a mean plasma EPO concentration of 0.5+/-0.9 IU/L. Thirty-seven patients treated with phlebotomy only had a mean plasma EPO concentration of 2.5+/-2.9 IU/L. The mean plasma EPO concentrations for 26 patients treated with hydroxyurea, 13 patients treated with radiophosphorous and 11 patients given a combination of myelosuppressive agents were 8.9+/-8.0, 10.9+/-12.6 and 7.2+/-7.4 IU/L, respectively. Untreated patients and patients on phlebotomy only had significantly lower values for plasma EPO than patients on therapy with myelosuppressive drugs. This finding persisted also after a correction for differences in haemoglobin levels had been introduced. Thereby, the present results would suggest a difference in the EPO feedback system in untreated and phlebotomised PV patients compared to PV patients treated with myelosuppressive agents.
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| 4. |
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| 5. |
- Cutts, Briony, 1976, et al.
(författare)
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Nf1 deficiency cooperates with oncogenic K-RAS to induce acute myeloid leukemia in mice.
- 2009
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 114:17, s. 3629-32
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Tidskriftsartikel (refereegranskat)abstract
- Hyperactive RAS signaling is caused by mutations in RAS genes or a deficiency of the neurofibromatosis gene (NF1) and is common in myeloid malignancies. In mice, expression of oncogenic K-RAS or inactivation of Nf1 in hematopoietic cells results in myeloproliferative disorders (MPDs) that do not progress to acute myeloid leukemia (AML). Because NF1 is a RAS-GTPase-activating protein it has been proposed that NF1 deficiency is functionally equivalent to an oncogenic RAS. It is not clear, however, whether Nf1 deficiency would be redundant in K-RAS-induced MPD development or whether the 2 mutations would cooperate in leukemogenesis. Here, we show that the simultaneous inactivation of Nf1 and expression of K-RAS(G12D) in mouse hematopoietic cells results in AML that was fatal in primary mice within 4 weeks and transplantable to sublethally irradiated secondary recipients. The data point to a strong cooperation between Nf1 deficiency and oncogenic K-RAS.
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| 6. |
- Grund, Sofia, et al.
(författare)
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The autocrine motility factor receptor is overexpressed on the surface of B cells in Binet C chronic lymphocytic leukemia.
- 2011
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Ingår i: Medical Oncology. - : Springer Science and Business Media LLC. - 1559-131X .- 1357-0560. ; 28:4, s. 1542-8
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Tidskriftsartikel (refereegranskat)abstract
- Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with a clinical spectrum reaching from discrete lymphocytosis to extensive enlargement of lymph nodes, spleen and liver, and bone marrow failure. The aim of this study was to identify genes that differentiate between patients with disease stage A vs. C according to Binet in order to better understand the disease. To achieve this, we performed DNA microarray analysis on B cells from CLL patients with stage A and C according to Binet and matched controls. Between CLL patients and controls, there were 1,528 differentially expressed genes and 360 genes were differentially expressed between Binet A and C patients. Due to the sheer number of regulated genes, we focused on the autocrine motility factor receptor (AMFR). AMFR has not previously been investigated in hematological disorders, but high expression of AMFR correlates with a more advanced stage and invasive potential in several human tumors. AMFR mRNA expression was higher in Binet A compared with Binet C patients (P=0.0053) and healthy controls (P=0.0051). Total AMFR protein was higher in Binet A patients compared to Binet C as analyzed by intracellular flow cytometry. However, AMFR exist both in the ER involved in protein degradation and on the cell surface involved in metastasis and cell motility. Cell surface AMFR was increased in Binet C compared with Binet A+B (P=0.016). In conclusion, the mRNA levels reflect the total amount of AMFR, whereas cell surface expression is associated with progression in CLL.
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| 7. |
- Hardling, Mats, et al.
(författare)
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Serial monitoring of BCR-ABL transcripts in chronic myelogenous leukemia (CML) treated with imatinib mesylate
- 2004
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Ingår i: Med Oncol. - 1357-0560. ; 21:4, s. 349-58
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Tidskriftsartikel (refereegranskat)abstract
- Survival among chronic myelogenous leukemia (CML) patients can be linked to the reduction in leukemic cell burden. Treatment with imatinib mesylate results in a high frequency of complete cytogenetic response, which can be further stratified using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). We have serially monitored peripheral blood and bone marrow BCR-ABL transcripts using qRT-PCR in CML patients commencing imatinib therapy, and compared the results with bone marrow cytogenetics. Seventeen patients (aged 25-74 yr) with Philadelphia chromosome positive CML in first chronic phase were treated with imatinib targeting a dose of 400 mg/d. The median follow up is 30 mo (range 9-33 mo). Every third month the product of the BCR-ABL fusion gene was evaluated in both blood and bone marrow specimens by real-time RT-PCR using the TaqMan probe system. In 113 simultaneously obtained blood and bone marrow samples, the BCR-ABL transcript values agreed well with cytogenetic data. Blood and bone marrow specimens gave comparable values for BCR-ABL transcripts. Before start of imatinib therapy there was a considerable variation in BCR-ABL transcripts among the patients, ranging approximately one log (base 10). Similarly, patients with a complete cytogenetic response following imatinib therapy had variable BCR-ABL transcript levels, ranging at least three logs (base 10). The major decline in BCR-ABL transcripts occurred within 6 mo after start of imatinib therapy. The decline in BCR-ABL transcripts, following imatinib therapy, appears to level off at 12-15 mo. Two late responders were identified with a still decreasing level in BCR-ABL transcripts after 24 mo of treatment. It is concluded that BCR-ABL mRNA quantification in peripheral blood is suitable for routine monitoring of the response to treatment and long-term disease status in CML, especially in patients who have achieved a complete cytogenetic response. A plateau in BCR-ABL transcripts seems to have been reached after 12-15 mo of imatinib treatment; however, some "late responders" are seen.
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| 9. |
- Jacobsson, Stefan, 1951, et al.
(författare)
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Flow cytometric analysis of megakaryocyte ploidy in chronic myeloproliferative disorders and reactive thrombocytosis.
- 1996
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Ingår i: European journal of haematology. - 0902-4441. ; 56:5, s. 287-92
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Tidskriftsartikel (refereegranskat)abstract
- Megakaryocyte (MK) ploidy patterns were analysed by flow cytometry in 29 newly diagnosed and previously untreated patients with chronic myeloproliferative disorders (MPD) and concomitant thrombocytosis, in 9 patients with reactive thrombocytosis (RT) and in 12 healthy individuals. Unfractionated bone marrow from routine aspirates was used. MKs were identified with a fluorescein labelled monoclonal antibody specific for glycoprotein IIIa (GPIIIa) and DNA was stained with propidium iodide. For the 12 healthy volunteers the mean modal ploidy number was 16 N; the 9 patients with RT displayed an identical MK ploidy pattern. The frequency of MKs with a ploidy > or = 32 N was 45% among the patients with essential thrombocythaemia (ET) compared to 32% among the healthy volunteers (p < 0.001). MKs with ploidy number > or = 64 N, comprising approximately 13% of the total number of MKs, was a characteristic finding in the patients with ET. Similar findings were present in 8 patients with polycythaemia vera (PV). In patients with PV 34% and 6% of the MKs displayed ploidies > or = 32 N and > or = 64 N, respectively. In contrast, a distinct shift towards lower ploidy number, with 63% of MKs < or = 8 N, was found among the 4 patients with chronic myeloid leukaemia (CML). The present results indicate that by using flow cytometric analysis of MK ploidy distribution in patients with thrombocytosis, those with a reactive cause are likely to be discriminated from patients with myeloproliferative thrombocytosis, i.e. PV and ET on one hand and CML on the other hand. The distinction between ET and PV, however, has to be made on other grounds.
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| 10. |
- Jacobsson, Stefan, 1951, et al.
(författare)
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Low megakaryocyte ploidy in Ph-positive chronic myelogenous leukemia measured by flow cytometry.
- 1999
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Ingår i: American journal of clinical pathology. - 0002-9173. ; 111:2, s. 185-90
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Tidskriftsartikel (refereegranskat)abstract
- In chronic myeloproliferative disorders, the megakaryocytes differ in size and maturation compared with those of healthy individuals. In the present study, by using a 2-color flow cytometry technique, we determined the frequency of bone marrow megakaryocytes in different ploidy classes in 13 newly diagnosed and untreated patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) and in 12 healthy volunteers. The results showed a significant difference in megakaryocyte ploidy distributions between these 2 study groups. On the average, patients with CML had 59% of their megakaryocytes in ploidy classes 2N to 8N; in contrast, the healthy volunteers had only 22% of their megakaryocytes in classes 2N to 8N. Two patients with complex Ph translocation and 2 patients with a small clone with a chromosome abnormality in addition to Ph had the same ploidy distribution as those with only Ph translocation. The platelet count did not correlate with the megakaryocyte mean ploidy.
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