Disease relevance of Myeloproliferative Disorders

• Following exposure to sublethal gamma-irradiation or N-ethyl-N-nitrosourea (ENU), MLL-CBP mice developed myelomonocytic hyperplasia and progressed to fatal myeloproliferative disorders [1].
• A recurrent somatic activating mutation in the nonreceptor tyrosine kinase JAK2 (JAK2V617F) occurs in the majority of patients with the myeloproliferative disorders polycythemia vera, essential thrombocythemia, myelofibrosis with myeloid metaplasia, and, less commonly, chronic myelomonocytic leukemia [2].
• Taken together, our data show that high and persistent TPO production by transduced hematopoietic cells in mice results in a fatal myeloproliferative disorder that has a number of features in common with human idiopathic myelofibrosis [3].
• Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder resulting from the neoplastic transformation of a hematopoietic stem cell [4].
• Frequent mutations in the GATA-1 gene in the transient myeloproliferative disorder of Down syndrome [5].

High impact information on Myeloproliferative Disorders

• Furthermore, Dok-1 or Dok-2 inactivation markedly accelerated leukemia and blastic crisis onset in Tec-p210bcr/abl transgenic mice known to develop, after long latency, a myeloproliferative disorder resembling human CML [6].
• Thus, oncogenic K-ras induces a myeloproliferative disorder but not AML, indicating that additional mutations are required for AML development [7].
• The NF1 tumor-suppressor gene is frequently inactivated in juvenile myelomonocytic leukemia, and Nf1 mutant mice model this myeloproliferative disorder (MPD) [8].
• Characterization of the platelet prostaglandin D2 receptor. Loss of prostaglandin D2 receptors in platelets of patients with myeloproliferative disorders [9].
• Adverse effect of erythropoietin in myeloproliferative disorders [10].

Chemical compound and disease context of Myeloproliferative Disorders

• PATIENTS: Patients with myeloproliferative disorders who were treated with hydroxyurea [11].
• Altered arachidonate metabolism by platelets in patients with myeloproliferative disorders [12].
• None of the STI571-treated mice were cured of the CML-like myeloproliferative disorder, however, and STI571-treated murine CML was transplanted to secondary recipients with high efficiency [13].
• Platelet function and thromboxane synthesis in myeloproliferative disorders [14].
• Development of a myeloproliferative disorder in a patient with monoclonal gammopathy of undetermined significance secreting immunoglobulin of the M class and treated with thalidomide and anti-CD20 monoclonal antibody [15].

Biological context of Myeloproliferative Disorders

• Decreased expression of c-MPL protein in platelets, increased expression of polycythemia rubra vera 1 (PRV-1) and nuclear factor I-B (NFIB) mRNA in granulocytes, and loss of heterozygosity on chromosome 9p (9pLOH) were described as molecular markers for myeloproliferative disorders (MPDs) [16].
• The analysis of rare chromosomal translocations in myeloproliferative disorders has highlighted the importance of aberrant tyrosine kinase signaling in the pathogenesis of these diseases [17].
• Cytogenetic, immunologic, and electron microscopic studies were performed on the blast cells of 28 pediatric patients with Down's syndrome, 13 with acute leukemia (DS-AL) and 15 with transient myeloproliferative disorders (DS-TMD) [18].
• HCK is located on human chromosome 20 at bands q11-12, a region that is affected by interstitial deletions in some acute myeloid leukemias and myeloproliferative disorders [19].
• Mutant N-ras induces myeloproliferative disorders and apoptosis in bone marrow repopulated mice [20].

Anatomical context of Myeloproliferative Disorders

• Fibroblast growth factor receptor 1 is fused to FIM in stem-cell myeloproliferative disorder with t(8;13) [21].
• Megakaryocytes from chronic myeloproliferative disorders show enhanced nuclear bFGF expression [22].
• Treatment of myeloproliferative disorders with hydroxyurea: effects on red blood cell geometry and deformability [23].
• Previously, we found that, in the myeloproliferative disorder polycythemia vera (PV), circulating erythroid progenitor cells were hypersensitive to insulin-like growth factor I (IGF-I), an effect shown to occur through the IGF-I receptor [24].
• A distinctive clonal myeloproliferative disorder, somewhat akin to chronic myeloid leukemia but with prominent erythroid and mast cell components, as well as granulocytic excess, was characterized [25].

Gene context of Myeloproliferative Disorders

• Somatic activation of oncogenic Kras in hematopoietic cells initiates a rapidly fatal myeloproliferative disorder [26].
• FGFR1, a transmembrane receptor tyrosine kinase for fibroblast growth factors, is constitutively activated by chromosomal translocations in an atypical stem-cell myeloproliferative disorder [27].
• Acquired mutations in GATA1 were detected in the vast majority of patients with acute megakaryoblastic leukemia (DS-AMKL) and in nearly every patient with transient myeloproliferative disorder (TMD), a "preleukemia" that may be present in as many as 10% of infants with DS [28].
• Similarly, the drug has now been shown to display equally impressive therapeutic activity in eosinophilia-associated chronic myeloproliferative disorders that are characterized by activating mutations of either the PDGFRB or the PDGFRA gene [29].
• Fusion of ETV6 to MDS1/EVI1 as a result of t(3;12)(q26;p13) in myeloproliferative disorders [30].

Analytical, diagnostic and therapeutic context of Myeloproliferative Disorders

• Adoptive transfer of Nf1-/- hematopoietic cells into irradiated mice induces a myeloproliferative disorder that did not respond to L-744,832 treatment [31].
• Chronic myelogenous leukemia (CML), a myeloproliferative disorder characterized by the clonal proliferation of a hematopoietic stem cell, is a malignancy for which allogeneic bone marrow transplantation (BMT), when available, constitutes a mainstay of treatment [32].
• These findings indicate that flow cytometric analysis of the density of neutrophil CD16 antigen is useful for the differential diagnosis of CML from other chronic myeloproliferative disorders [33].
• Hematopoietic cell transplantation for adult patients with myelodysplastic syndromes and myeloproliferative disorders [34].
• Increased low-density lipoprotein levels after splenectomy: a role for the spleen in cholesterol metabolism in myeloproliferative disorders [35].

References