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- Andréasson, Björn, 1956
(författare)
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Clinical and experimental studies in polycythemia vera and essential thrombocythemia
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- It is widely accepted that the diagnoses of polycythemia vera (PV) and essential throbocythemia (ET) are based upon the Polycythemia Vera Study Group criteria. These criteria are, however, of non-specific character and during the recent years more specific criteria have been proposed. In the present work the diagnostic potential of plasma erythropoietin (EPO), EPO-independent erythroid colony (EEC) growth, the stem cell antigen CD34 and thrombopoietin (TPO) were studied. The influence of different myelosuppressive agents on these variables was investigated.The concentration of CD34 positive (CD34+) cells was found to be significantly elevated in peripheral blood (PB) in PV patients compared to healthy controls. This difference was, however, not present in material from aspirated bone marrow (BM) or BM material obtained by biopsy. CD34+ cells were significantly elevated in PV patients with long disease duration and in patients with advanced disease. Also in PB of untreated ET patients CD34+ cells were significantly higher compared with controls.In vitro growth of EEC from BM progenitor cells was present in all PV patients studied. A majority of both PV and ET patients presented EEC growth when PB was used as a progenitor cell source.In all untreated PV patients the plasma EPO concentration was below the lower reference limit. About 50% of the untreated ET patients also had subnormal plasma EPO.No significant differences in plasma TPO concentrations were present when PV patients and healthy controls were compared. The mean plasma TPO concentration in ET patients significantly exceeded the mean for controls. The ET patients with subnormal plasma EPO had significantly lower plasma TPO compared with ET patients with normal or high plasma EPO. There was no significant difference between the ET patients with subnormal plasma EPO and controls.The mean plasma EPO did not rise above the lower reference limit when hemoglobin concentrations were normalized by phlebotomy treatment in PV patients. PV patients treated with different myelosuppressive agents, i.e. hydroxyurea (HU), radiophophorus (32P) or combinations of different cytostatics, presented significantly higher plasma EPO concentration compared with both untreated and phlebotomy treated PV patients. ET patients treated with HU, 32P, a-interferon or combinations of different cytostatics had significantly higher mean plasma EPO compared with untreated ET patients, also when correction for differences in hemoglobin levels were undertaken.PV patients on phlebotomy treatment only had higher concentrations of CD34+ cells and EEC growth compared with PV patients treated with HU. There was no significant difference in TPO concentration between PV on phlebotomy therapy and patients on myelosuppressive agents. Untreated ET patients had significantly higher CD34+ cell concentration and EEC growth compared with ET patients treated with HU. Untreated ET patients presented significantly lower plasma TPO concentrations compared with ET patients on myelosuppressive agents.Plasma EPO concentration should be used as a diagnostic criterion in the diagnosis of PV. Subnormal plasma EPO in ET is a valuable support for diagnosis and yields important information inasmuch as these patients have need for early initiation of myelosuppressive treatment due to high risk for vascular complications. EEC growth in PV and ET has good diagnostic potential and should be included as a diagnostic criterion. The concentration of CD34+ cells is not specific enough to be a diagnostic criterion in PV or ET but could be used as a proliferation marker in PV. Plasma TPO concentration can not be used as a diagnostic tool in PV or ET. There seems to be a relation between TPO and EPO in ET patients. ET patients with normal or high plasma EPO have high plasma TPO. In these patients TPO could even be the cause of platelet elevation.
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| 2. |
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| 3. |
- Constantinescu, Radu, 1966, et al.
(författare)
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Proteomic profiling of cerebrospinal fluid in parkinsonian disorders.
- 2010
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Ingår i: Parkinsonism & related disorders. - : Elsevier BV. - 1873-5126 .- 1353-8020. ; :16, s. 545-49
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson's disease (PD) and atypical parkinsonian disorders (APD), including multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), are a group of neurodegenerative diseases sharing many similar signs and symptoms but distinguished by their particular clinical features, treatment response, prognosis and mortality. The differential diagnosis may be challenging, especially in early disease stages. Considering the importance of an accurate diagnosis both for clinical management and for research, new diagnostic tools are needed. In this study, we investigated 56 PD, 42 MSA, 39 PSP, 9 CBD patients, and 24 healthy controls. After screening the cerebrospinal fluid (CSF) proteome using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), we identified 4 proteins (ubiquitin [mass-to-charge ratio (m/z) 8590], beta2-microglobulin [m/z 11730], and 2 secretogranin 1 [chromogranin B] fragments [m/z 7260 and m/z 6250]) that differentiated healthy controls and PD patients from patients with APD. However, they could not differentiate PD patients from controls. As none of these changes were APD subgroup-specific, they most likely reflect the intensity and/or extent of the neurodegenerative process in general.
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| 4. |
- Johansson, Peter, 1958, et al.
(författare)
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Increased risk for vascular complications in PRV-1 positive patients with essential thrombocythaemia.
- 2003
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Ingår i: British journal of haematology. - 0007-1048. ; 123:3, s. 513-6
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Tidskriftsartikel (refereegranskat)abstract
- Essential thrombocythaemia (ET) is a heterogeneous disorder with respect to plasma erythropoietin concentration at diagnosis and clonality of haematopoiesis. Polycythaemia rubra vera-1 (PRV-1) positivity, i.e. PRV-1 mRNA overexpression, is known to be present in the vast majority of patients with polycythaemia vera and also in some patients with ET. In the present study, PRV-1 expression was quantified by real-time polymerase chain reaction in 70 ET patients; 17 of them (24%) were found to be PRV-1 positive. Ten of the 17 PRV-1 positive ET patients had experienced thromboembolic complications compared with 14 of 53 PRV-1 negative patients, the difference between the two groups being statistically significant (P=0.02). In addition, the frequency of total vascular complications, thromboembolic events and major bleedings, was significantly higher in the group of PRV-1 positive as compared with PRV-1 negative ET patients (P=0.03). The time from diagnosis of ET to the requirement of platelet-lowering therapy was significantly shorter in PRV-1 positive compared with PRV-1 negative ET patients (P=0.014). It can be concluded that PRV-1 positive patients appear to suffer from a more aggressive disorder with increased risk for vascular complications and a greater need for platelet-lowering therapy, compared with PRV-1 negative ET patients.
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| 5. |
- Johansson, Peter, 1958, et al.
(författare)
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The presence of a significant association between elevated PRV-1 mRNA expression and low plasma erythropoietin concentration in essential thrombocythaemia.
- 2003
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Ingår i: European journal of haematology. - 0902-4441. ; 70:6, s. 358-62
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Tidskriftsartikel (refereegranskat)abstract
- Approximately 45% of newly diagnosed patients with essential thrombocythaemia (ET) demonstrate subnormal plasma erythropoietin (EPO) concentrations, which constitutes a risk factor for occlusive vascular events. In 58 ET patients, a possible association between polycythaemia rubra vera-1 (PRV-1) overexpression and subnormal plasma EPO was investigated, which was always measured prior to the institution of platelet lowering agents. At the time when PRV-1 expression was measured, 28 of 58 (48%) ET patients had received platelet lowering treatment. PRV-1 expression was measured by quantitative real-time reverse transcription-polymerase chain reaction assay of mRNA extracted from purified peripheral blood buffy coat. The cycle threshold (CT) value of PRV-1 was determined and was divided with the CT value for the housekeeping GAPDH gene transcript. A quotient <0.93 was defined as PRV-1 positive. Of the ET patients 12 of 58 (21%) were PRV-1 positive and 19 of 58 (33%) demonstrated subnormal plasma EPO. In the 58 ET patients there was a significant association between low plasma EPO and PRV-1 positive results (P = 0.001). The 30 ET patients who had not received any platelet lowering treatment showed a significant (P = 0.005) relation between PRV-1 positivity and subnormal plasma EPO. No such relationship was present in the 28 ET patients who had received prior treatment with the above drugs (P = 0.147).
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| 6. |
- Karlsson, Johanna, 1973, et al.
(författare)
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Pneumococcal vaccine responses in elderly patients with multiple myeloma, Waldenstrom’s macroglobulinemia, and monoclonal gammopathy of undetermined significance
- 2013
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Ingår i: Trials in vaccinology. - : Elsevier BV. - 1879-4378. ; 2, s. 31-38
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Tidskriftsartikel (refereegranskat)abstract
- Background Vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPV) has been recommended for elderly patients with B cell malignancies and dysfunctions because of their enhanced susceptibility to pneumococcal infections. More recent recommendations advocate the use of conjugate pneumococcal vaccines. Methods We compared responses to single dose vaccination with either PPV or the 7-valent pneumococcal conjugate vaccine (PCV7) in fifty-six patients ⩾60 years with a diagnosis of multiple myeloma (n = 24), Waldenstrom’s macroglobulinemia (n = 15) and the non-malignant B cell disorder monoclonal gammopathy of undetermined significance (MGUS) (n = 17), and 20 age-matched controls. Serum was collected prior to vaccination and 4–8 weeks later, and analyzed for IgG antibody levels to pneumococcal serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F by ELISA. Functional antibody activity towards pneumococcal serotypes 4 and 14 was measured using an opsonophagocytic killing assay (OPA). Results All patient groups had lower pre-vaccination IgG antibody and OPA titers to the investigated serotypes compared to the healthy controls. Following vaccination, myeloma patients responded with significant IgG titer increases to 1/7 serotypes and OPA titer increases to 1/2 serotypes. Corresponding IgG and OPA vaccine responses were 3/7 and 0/2 for Waldenstrom patients, 4/7 and 1/2 for MGUS patients, and 4/7 and 2/2 for the healthy controls, respectively. Notably high antibody levels without corresponding OPA titers were seen among a few myeloma patients indicating the presence of non-functional antibodies. Neither of the two vaccines elicited significantly higher serotype-specific IgG concentrations, OPA titers or antibody fold increases in any of the study groups. Hypogammaglobulinemia and ongoing chemotherapy were associated with poor vaccine responses in a multivariate analysis. Conclusion Our findings confirm that B cell malignancies and disorders among elderly patients are associated with suboptimal responses to pneumococcal vaccination. Single-dose PCV7 was not shown to be superior to PPV.
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| 7. |
- Pettersson, Helna, et al.
(författare)
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The clinical relevance of broad mutational screening of myeloproliferative neoplasms at diagnosis.
- 2023
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Ingår i: Frontiers in oncology. - 2234-943X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Myeloproliferative neoplasm (MPN) is a heterogenous group of hematological malignancies including polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). JAK2V617F is the most frequent driver mutation in all three entities, but in PMF and ET mutations in CALR and MPL are also frequent. Mutations seen in additional genes are also often the same regardless of subtype of MPN. The aim of this study was to analyze a population based MPN cohort for genetic variants with prognostic value that can guide clinical decisions.MPN patients from Western Sweden diagnosed between 2008-2013 (n=248) were screened for mutations in 54 genes associated with myeloid malignancy.Mutations in the genes SRSF2 and U2AF1 correlated significantly with impaired overall survival but did not correlate to increased risk for vascular events, neither before nor after diagnosis. Rather, mutations in these genes showed an association with disease transformation. Several recurrent gene variants with allele frequency close to 50% were confirmed to be germline. However, none of these variants was found to have an earlier onset of MPN.In conclusion, we identified gene mutations to be independent markers of impaired survival in MPN. This indicates the need for more individualized assessment and treatment of MPN patients and a wider gene mutation screening already at diagnosis. This could ensure the identification of patients with high-risk mutations early on. In addition, several genetic variants were also identified as germline in this study but gave no obvious clinical relevance. To avoid conclusions from non-informative genetic variants, a simultaneous analysis of normal cell DNA from patients at diagnosis should be considered.
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