Disease relevance of Myeloid Metaplasia

• Single-agent thalidomide (THAL) at "conventional" doses (> 100 mg/d) has been evaluated in myelofibrosis with myeloid metaplasia (MMM) based on its antiangiogenic properties and the prominent neoangiogenesis that occurs in MMM [1].
• Recently, we and others identified a single recurrent somatic activating mutation (JAK2V617F) in the Janus kinase 2 (JAK2) tyrosine kinase in the myeloproliferative disorders (MPDs) polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis [2].
• Low-dose thalidomide ameliorates cytopenias and splenomegaly in myelofibrosis with myeloid metaplasia: a phase II trial [3].
• A missense somatic mutation in JAK2 gene (JAK2 V617F) has recently been reported in chronic myeloproliferative disorders, including polycythemia vera, essential thrombocythemia and myelofibrosis with myeloid metaplasia, strongly suggesting its role in the pathogenesis of myeloid disorders [4].
• Characterization of the hypocholesterolemia observed in polycythemia vera and agnogenic myeloid metaplasia revealed significant reductions in plasma total cholesterol, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol in an age- and sex-matched comparison with the Framingham population [5].

High impact information on Myeloid Metaplasia

• A phase 2 trial of combination low-dose thalidomide and prednisone for the treatment of myelofibrosis with myeloid metaplasia [1].
• FLT3 internal tandem duplication mutations are rare in agnogenic myeloid metaplasia [6].
• In view of the known cooperativity between CSF-1 and other growth factors in regulating hematopoiesis, the finding of increased serum CSF-1 concentrations and its association with myeloid metaplasia and bone marrow extension may indicate a pathophysiologic role for CSF-1 in determining the phenotypic expression of MPD [7].
• Increased circulating CSF-1 (M-CSF) in myeloproliferative disease: association with myeloid metaplasia and peripheral bone marrow extension [7].
• The glucose-6-phosphate dehydrogenase (G-6-PD) types and chromosomes of hematopoietic and other tissues were determined in a woman with agnogenic myeloid metaplasia [8].

Chemical compound and disease context of Myeloid Metaplasia

• The myeloid metaplasia usually observed in the spleen after idarubicin treatment was absent in mice co-treated with imatinib [9].
• In vitro antiproliferative activity of the farnesyltransferase inhibitor R115777 in hematopoietic progenitors from patients with myelofibrosis with myeloid metaplasia [10].
• Splenic irradiation in the treatment of patients with chronic myelogenous leukemia or myelofibrosis with myeloid metaplasia. Results of daily and intermittent fractionation with and without concomitant hydroxyurea [11].
• The responses of 23 patients with agnogenic myeloid metaplasia (AMM) to androgen therapy were studied [12].
• The relationship between the extent of bone marrow reticulin and collagen fibrosis and the concentration of granulocytic (CFU-GM), erythroid (BFU-E) and megakaryocyte (CFU-Mk) progenitor cells in the peripheral blood of patients with primary agnogenic myeloid metaplasia (AMM) and secondary myelofibrosis (sMF) has not been definitively correlated [13].

Biological context of Myeloid Metaplasia

• RESULTS: Two patients showed sinusoidal PHT (increased hepatic venous pressure gradient), normal portal flow, and massive myeloid metaplasia of the liver [14].
• Histology revealed a steroid cell tumor with foci of myeloid metaplasia; bony trabecula formation was present [15].

Anatomical context of Myeloid Metaplasia

• Circulating CD34+, CD133+, and vascular endothelial growth factor receptor 2-positive endothelial progenitor cells in myelofibrosis with myeloid metaplasia [16].
• Neutrophils from patients with myeloid metaplasia show a pattern of defective microbial killing, high alkaline phosphatase activity and low myeloperoxidase activty which is similar to that seen in severe infections and distinct from chronic granulocytic leukaemia [17].
• Each course of GM-CSF induced a rapid and tremendous increase in leukocyte count as well as in spleen size, 111indium chloride scanning suggested a myeloid metaplasia of the spleen [18].

Gene context of Myeloid Metaplasia

• Plasma matrix metalloproteinase and tissue inhibitor of metalloproteinase in patients with agnogenic myeloid metaplasia or idiopathic primary myelofibrosis [19].
• PURPOSE: Tumor necrosis factor-alpha (TNF-alpha) is an important effector and regulatory cytokine involved in the pathophysiology of hematologic malignancies, including hairy cell leukemia (HCL), chronic lymphocytic leukemia (CLL), agnogenic myeloid metaplasia (AMM) and Philadelphia-negative myeloproliferative disorders (MPD) [20].
• Importance of plasma matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinase (TIMP) in development of fibrosis in agnogenic myeloid metaplasia [21].
• Blood thrombopoietin, IL-6 and IL-11 levels in patients with agnogenic myeloid metaplasia [22].
• Bone marrow expression of vascular endothelial growth factor in myelofibrosis with myeloid metaplasia [23].

Analytical, diagnostic and therapeutic context of Myeloid Metaplasia

• Durable responses to thalidomide-based drug therapy for myelofibrosis with myeloid metaplasia [24].
• BACKGROUND: Allogeneic hematopoietic stem cell transplantation is potentially curative in agnogenic myeloid metaplasia (AMM) but is associated with substantial mortality and morbidity that necessitates accurate identification of patients in whom benefit outweighs risk [25].
• In a 5-year period 37 patients with auto-immune thrombocytopenic purpura (AITP) and 22 with agnogenic myeloid metaplasia (AMM) underwent splenectomy [26].

References