Disease relevance of Myelofibrosis

• Phase 2 trial of imatinib mesylate in myelofibrosis with myeloid metaplasia [1].
• More on Myb in myelofibrosis: molecular analyses of MYB and EP300 in 55 patients with myeloproliferative disorders [2].
• Essential thrombocythemia (ET) and idiopathic myelofibrosis (PMF) are two myeloproliferative diseases characterized by a marked megakaryocytic (MK) involvement [3].
• The pivotal role of transforming growth factor beta 1 (TGF-beta 1) in the pathogenesis of myelofibrosis has been documented, but the mechanisms mediating osteosclerosis remain unclear [4].
• Most patients with polycythemia vera and half with idiopathic myelofibrosis and essential thrombocythemia have an acquired V617F mutation in JAK2 [5].

High impact information on Myelofibrosis

• Stem-cell transplantation for myelofibrosis [6].
• High-dose intravenous methylprednisolone for idiopathic myelofibrosis [7].
• Clinical evidence for 1,25-dihydroxycholecalciferol action in myelofibrosis [8].
• Myelofibrosis associated with rubidazone [9].
• Ten patients with bone-marrow failure from myelofibrosis, aplastic anaemia, paroxysmal nocturnal haemoglobinuria, and "hairy cell" leukaemia, who had failed to respond to androgens and/or glucocorticosteroids, were treated with a combination of aetiocholanolone and prednisolone [10].

Chemical compound and disease context of Myelofibrosis

• A fluorescein-labelled anti-human immunoglobulin was used to demonstrate that peripheral blood from patients with myelofibrosis had a high proportion of phagocytic cells containing fluorescent immune complexes [11].
• Myelofibrosis or increased bone marrow reticulin are a prominent aspect in most patients with M7 [12].
• Serious myeloproliferative reactions associated with the use of thalidomide in myelofibrosis with myeloid metaplasia [13].
• Urinary hydroxyproline excretion in myelofibrosis [14].
• A somatic mutation in the JH2 autoinhibitory domain of the Janus kinase 2 (JAK2) tyrosine kinase was recently described in polycythemia vera, essential thrombocythemia, and myelofibrosis with myeloid metaplasia [15].

Biological context of Myelofibrosis

• High levels of circulating CD34 cells, dacrocytes, clonal hematopoiesis, and JAK2 mutation differentiate myelofibrosis with myeloid metaplasia from secondary myelofibrosis associated with pulmonary hypertension [16].
• Deletion of megakaryocytic-specific regulatory sequences of GATA-1 (Gata1(tm2Sho) or GATA-1(low) mutation) results in severe thrombocytopenia, because of defective thrombocytopoiesis, and myelofibrosis [17].
• IL-8 and its CXCR1 and CXCR2 receptors participate in the control of megakaryocytic proliferation, differentiation, and ploidy in myeloid metaplasia with myelofibrosis [18].
• NF-kappa B as a central mediator in the induction of TGF-beta in monocytes from patients with idiopathic myelofibrosis: an inflammatory response beyond the realm of homeostasis [19].
• Unusual indium-111 accumulation and extramedullary hematopoiesis in the lungs of a patient with idiopathic myelofibrosis are described [20].

Anatomical context of Myelofibrosis

• Serum from patients with myelofibrosis incubated with polymorphs from healthy subjects caused the appearance of inclusions similar to those found when the patients' own cells were used, the healthy phagocytes apparently engulfing complexes from the patients' sera [11].
• Abnormalities of GATA-1 in megakaryocytes from patients with idiopathic myelofibrosis [21].
• Patients with autoimmune myelofibrosis universally have a positive ANA test and frequently have either elevated anti-DNA titers or a positive LE cell preparation [22].
• Extramedullary hematopoietic ascitic fluid cytology in myelofibrosis [23].
• A prospective pilot study was performed to evaluate the effect of reduced-intensity conditioning with busulphan (10 mg/kg), fludarabine (180 mg/qm) and anti-thymocyte globulin followed by allogeneic stem cell transplantation from related (n = 8) and unrelated donors (n = 13) in 21 patients with myelofibrosis [24].

Gene context of Myelofibrosis

• Interestingly, one of the patients with SM and the patient with CNL with JAK2 V617F had a history of lymphoma, and this patient with SM also had associated myelofibrosis and CMML [15].
• A pathobiologic pathway linking thrombopoietin, GATA-1, and TGF-beta1 in the development of myelofibrosis [25].
• Prominent role of TGF-beta 1 in thrombopoietin-induced myelofibrosis in mice [26].
• Etanercept, a soluble tumor necrosis factor receptor, palliates constitutional symptoms in patients with myelofibrosis with myeloid metaplasia: results of a pilot study [27].
• Dysregulation and overexpression of HMGA2 in myelofibrosis with myeloid metaplasia [28].

Analytical, diagnostic and therapeutic context of Myelofibrosis

• In conclusion, impaired GATA-1 expression may contribute to the development of myelofibrosis, and the GATA-1(low) mutants may represent a suitable animal model for the human disease that may shed light on its pathogenesis [29].
• Thus, allogeneic hematopoietic cell transplantation offers long-term relapse-free survival for patients with myelofibrosis [30].
• Although more clinical trials are needed, Kaposi' s sarcoma and myelofibrosis represent other malignancies in which thalidomide has already demonstrated promising activity [31].
• Major effects of TPO delivered by a single injection of a recombinant adenovirus on prevention of septicemia and anemia associated with myelosuppression in mice: risk of sustained expression inducing myelofibrosis due to immunosuppression [32].
• 2-Chlorodeoxyadenosine treatment after splenectomy in patients who have myelofibrosis with myeloid metaplasia [33].

References