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Myeloproliferative Disease (myeloproliferative + disease)

Distribution by Scientific Domains
Medical Sciences77%

Kinds of Myeloproliferative Disease

  • chronic myeloproliferative disease
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    Selected Abstracts

    HSPA1A is an important regulator of the stability and function of ZNF198 and its oncogenic derivative, ZNF198,FGFR1

    JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2007
    Chitta S. Kasyapa
    Abstract Mass spectroscopy analysis demonstrated that the HSPA1A protein is found in complex with the ZNF198 protein which is involved in a chromosome rearrangement with the FGFR1 gene in an atypical myeloproliferative disease. HSPA1A is a member of the HSP70 family of genes which has been shown to be inducible in a variety of circumstances. Exogenous expression of the ZNF198,FGFR1 fusion kinase gene as well as ZNF198 in a model cell system results in a large (>650-fold) increase in HSP70 mRNA levels. Using KNK437, a specific inhibitor of HSP70 transcription, we have demonstrated that an important function of HSPA1A is to stabilize the ZNF198 and ZNF198,FGFR1 proteins. In the absence of HSPA1A, specific functions of ZNF198,FGFR1 such as STAT3 phosphorylation is also lost. Treatment of cells with KNK437 in the presence of MG132, an inhibitor of proteasomal degradation of proteins, suggested that only the ZNF198,FGFR1 protein is subject to the proteasomal degradation pathway, while ZNF198 is not. These observations suggest an important role for HSPA1A in ZNF198 and ZNF198,FGFR1 mediated cellular function. J. Cell. Biochem. 102: 1308,1317, 2007. © 2007 Wiley-Liss, Inc. [source]

    JAK2V617F mutation in patients with arterial thrombosis in the absence of overt myeloproliferative disease

    JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2009
    F. DENTALI
    [source]

    Juvenile myelomonocytic leukemia with t(7;11)(p15;p15) and NUP98-HOXA11 fusion,

    AMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2009
    Yoko Mizoguchi
    The t(7;11)(p15;p15) translocation has been reported as a rare and recurrent chromosomal abnormality in acute myeloid leukemia (AML) patients. The NUP98-HOXA9 fusion gene with t(7;11)(p15;p15) was identified and revealed to be essential for leukemogenesis and myeloproliferative disease. To date, t(7;11)(p15;p15) with NUP98-HOXA11 fusion has been reported only in one case of ph-negative chronic myeloid leukemia (CML). Here, we report a case of a 3-year-old girl with juvenile myelomonocytic leukemia (JMML) carrying t(7;11)(p15;p15) abnormality with NUP98-HOXA11 fusion. AML chemotherapy followed by bone marrow transplantation (BMT) was found to be effective in treating this disorder, and she remains in complete remission for 3 years after BMT. We suggest the possibility that AML chemotherapy might be effective for treating JMML with t(7;11)(p15;p15) abnormality and NUP98-HOXA11 fusion. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc. [source]

    Phosphorylation of the SSBP2 and ABL proteins by the ZNF198-FGFR1 fusion kinase seen in atypical myeloproliferative disorders as revealed by phosphopeptide-specific MS

    PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 16 2009
    Chitta Kasyapa
    Abstract The ZNF198-fibroblast growth factor receptor-1 (FGFR1) fusion kinase is a constitutively activated tyrosine kinase associated with a specific atypical myeloproliferative disease. The chimeric protein localizes to the cytoplasm, unlike the wild type FGFR1 receptor kinase, and presumably inappropriately phosphorylates specific targets as part of the oncogenic signaling cascade. Other than known targets of the FGFR1 kinase itself, few specific targets of ZNF198-FGFR1 have been identified. Using a genetically engineered HEK 293 cell system, we have identified proteins that are specifically phosphorylated in the presence of the fusion kinase using anti-phosphotyrosine immunoprecipitation and MS. Compared with 293 cells expressing exongenous wild type FGFR1, ZNF198-FGFR1 is associated with phosphorylation of several proteins including SSBP2, ABL, FLJ14235, CALM and TRIM4 proteins. The specificity of the phosphorylation events in the SSBP2 and ABL proteins, which have previously been implicated in leukemogenesis, was further confirmed independently using immunoprecipitation with protein-specific antibodies and Western blotting. The MS analysis also identified the phosphorylation events in the ZNF198 moiety in the chimeric protein that might be related to its function. These studies identify the intersection of several different leukemia-related pathways in the development of this myeloproliferative disorder and provide new insights into the substrates of FGFR1 under defined conditions. [source]

    Improvement of fibrosis in a patient with chronic myeloproliferative disease

    BRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2007
    Andrew Retter
    No abstract is available for this article. [source]

    Mechanisms of constitutive activation of Janus kinase 2-V617F revealed at the atomic level through molecular dynamics simulations

    CANCER, Issue 8 2009
    Tai-Sung Lee PhD
    Abstract BACKGROUND: The tyrosine kinase Janus kinase 2 (JAK2) is important in triggering nuclear translocation and regulation of target genes expression through signal transducer and activator of transcription pathways. The valine-to-phenylalanine mutation at amino acid 617 (V617F), which results in the deregulation of JAK2, has been implicated in the oncogenesis of chronic myeloproliferative disease. However, both the mechanism of JAK2 autoinhibition and the mechanism of V617F constitutive activation remain unclear. METHOD: In this work, the authors used molecular dynamics simulation techniques to establish plausible mechanisms of JAK2 autoinhibition and V617F constitutive activation at the atomic level. RESULTS: In wild-type JAK2, the activation loop of JAK2-homology domain 1 (JH1) is pulled toward the JH1/JH2 interface through interactions with key residues of JH2, especially S591, F595, and V617, and stabilizes the inactivated form of JH1. In the case of V617F, through the aromatic ring-ring stacking interaction, F617 blocks the interaction of JH1 the activation loop, S591, and F595, thus causing the JH1 activation loop to move back to its activated form. CONCLUSIONS: The current results indicated that this simulation-derived mechanism of JAK2 autoregulation is consistent with current available experimental evidence and may lead to a deeper understanding of JAK2 and other kinase systems that are regulated by pseudokinases. Cancer 2009. © 2009 American Cancer Society. [source]

    Acute promyelocytic leukemia developing in untreated essential thrombocythemia

    AMERICAN JOURNAL OF HEMATOLOGY, Issue 2 2002
    Naoaki Sato
    Abstract We describe a patient with untreated essential thrombocythemia (ET) who developed microgranular variant of acute promyelocytic leukemia, 9 years after the initial diagnosis of ET. He achieved complete remission (CR) but relapsed 11 months later. After achieving the second CR, he received peripheral stem cell transplantation from his HLA complete-matched sibling. Five months after the transplantation, he relapsed again with meningeal infiltration of leukemic cells. In this paper, we review cases of promyelocytic transformation of myeloproliferative diseases (MPD) other than chronic myeloid leukemia (CML). To our knowledge, this is the first case of promyelocytic transformation of Philadelphia chromosome negative untreated ET, in whom both t(15;17) and PML-RAR, fusion were proven. Am. J. Hematol. 71:114,116, 2002. © 2002 Wiley-Liss, Inc. [source]

    Serum interleukin (IL)-1, IL-2, sIL-2Ra, IL-6 and thrombopoietin levels in patients with chronic myeloproliferative diseases

    BRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2005
    Katerina E. Panteli
    Summary A number of growth factors are involved in clonal haematopoietic expansion and their clinical significance in patients with chronic myeloproliferative diseases requires further evaluation. Using enzyme-linked immunosorbent assays, we analysed serum levels of interleukin (IL)-1a, IL-1b, IL-2, IL-6, the soluble IL-2 receptor alpha (sIL-2Ra), and thrombopoietin (TPO), in 25 individuals with myelofibrosis with myeloid metaplasia (MMM), 40 with essential thrombocythaemia (ET), eight with polycythaemia vera (PV), 10 patients with chronic myeloid leukaemia (CML) and 27 normal controls. These were correlated with clinicopathological characteristics including overall survival, and histopathological bone marrow features, including angiogenesis. The serum derived from patients with MMM, ET, PV and CML contained significantly higher IL-2 and sIL-2Ra than healthy subjects, while IL-6 levels were higher only in MMM and CML than controls. IL-2, sIL-2Ra and IL-6 levels were raised during the transformation phase of CML, during progression of MMM to AML, and ET and PV to myelofibrosis (P < 0·001). There was a positive correlation between IL-2, sIL-2Ra, IL-6 and angiogenesis in bone marrow samples. Cytokines may be useful markers for predicting clinical evolution, reflecting increased angiogenesis. This requires further evaluation to guide diagnostic and therapeutic options. [source]