Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032463 (polycythemia vera)
 3,374 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Standardized bone marrow (BM) features determined by semiquantitative scoring are valuable tools for the recognition and easily reproducible interpretation of histological patterns in hematopathology. This procedure may help to characterize various disease entities, but especially to differentiate chronic myeloproliferative disorders (MPDs) with increased platelet counts from reactive thrombocytosis (RTh). A clear-cut separation of these conditions continues to present a major problem in hematology. Therefore MPDs are a most suitable model to test the diagnostic relevance of this procedure. By regarding the literature and based on archive material that involved BM biopsies of 319 patients, a semiquantitative grading of histological parameters was performed. Standardized features were applied for a stepwise discriminant analysis to establish different sets of variables exerting a diagnostic impact. A distinction into five histological patterns was achieved that showed a correctly predicted group membership of about 94 %. These were consistent with the clinicopathological diagnosis of polycythemia vera, essential thrombocythemia (ET), prefibrotic or early fibrotic chronic idiopathic myelofibrosis (CIMF) and finally RTh. Variables of discriminating potency according to their ranking included megakaryopoiesis (maturation defects, nuclear lobulation, naked and bulbous nuclei, small and giant size), reticulin fibers, erythro- and granulopoiesis (left shifting and quantity) and cellularity. These findings are in keeping with the assumption that characteristic patterns of BM histopathology can be assigned to different subtypes of MDPs mimicking ET. Discrimination between ET and especially early stage CIMF with thrombocythemia is warranted because of significant implications concerning therapeutic strategies, follow-up examinations and survival. Regarding these results, a schematic procedure is proposed to be used for daily routine diagnosis concerning the discrimination of MPDs.
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PMID:Standardization of bone marrow features--does it work in hematopathology for histological discrimination of different disease patterns? 1573 66

Clonal aberrations leading to gain of 9p--mostly due to trisomy 9--are often reported in polycythemia vera. We report on four cases of chronic myeloproliferative disorders that demonstrated a new recurrent unbalanced rearrangement between chromosomes 9 and 18 leading to trisomy of 9p and a monosomy of 18p. This abnormality was confirmed with fluorescence in situ hybridization using chromosome painting and locus-specific probes. Three cases were diagnosed as polycythemia vera; one case presented with secondary acute myeloid leukemia following idiopathic osteomyelofibrosis. The prognostic impact of this unbalanced aberration and of gains of 9p in chronic myeloproliferative disorders remains to be clarified.
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PMID:Gain of 9p due to an unbalanced rearrangement der(9;18): a recurrent clonal abnormality in chronic myeloproliferative disorders. 1599 76

Contrasting the circulating CD34+ hematopoietic progenitor cells (HPCs) in chronic myeloproliferative disorders (CMPDs), scant knowledge is available regarding their quantity in the bone marrow (BM). Therefore, a clinicopathological study was performed on trephine biopsies in 575 patients with CMPDs focused on chronic idiopathic myelofibrosis (CIMF). A comparison with 25 healthy subjects revealed no significant differences in the numbers of HPCs (6 +/- 3/mm2) in polycythemia vera, essential thrombocythemia and advanced fibro-osteosclerotic stages of CIMF. Pre-fibrotic and early-stage CIMF displayed 16 +/- 11 precursors per mm2 BM. Sequential biopsies in this disorder showed a decline in HPCs (10 +/- 6/mm2) with evolving myelofibrosis-myeloid metaplasia (MMM), while in terminal stages acceleration generated an increase (24 +/- 25/mm2). A significant association between the quantity of HPCs and the development of myelofibrosis, splenomegaly, and anemia as well as an increase in peripheral blasts was recognizable in CIMF. Moreover, in all subtypes of CMPDs, a favorable prognosis was significantly associated with a higher number of HPCs in the BM. In conclusion, enhanced inflow of precursors from the BM with subsequent trapping, self-renewal and mobilization by the spleen is assumed to indicate a progressive generalization and worsening of the outcome. This putative pathomechanism is significantly associated with the evolution of MMM.
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PMID:Bone marrow CD34+ progenitor cells in Philadelphia chromosome-negative chronic myeloproliferative disorders--a clinicopathological study on 575 patients. 1601 8

An activating 1849G>T mutation of JAK2 (Janus kinase 2) tyrosine kinase was recently described in chronic myeloproliferative disorders (MPDs). Its role in other hematologic neoplasms is unclear. We developed a quantitative pyrosequencing assay and analyzed 374 samples of hematologic neoplasms. The mutation was frequent in polycythemia vera (PV) (86%) and myelofibrosis (95%) but less prevalent in acute myeloid leukemia (AML) with an antecedent PV or myelofibrosis (5 [36%] of 14 patients). JAK2 mutation was also detected in 3 (19%) of 16 patients with Philadelphia-chromosome (Ph)-negative chronic myelogenous leukemia (CML), 2 (18%) of 11 patients with megakaryocytic AML, 7 (13%) of 52 patients with chronic myelomonocytic leukemia, and 1 (1%) of 68 patients with myelodysplastic syndromes. No mutation was found in Ph(+)CML (99 patients), AML M0-M6 (28 patients), or acute lymphoblastic leukemia (20 patients). We conclude that the JAK2 1849G>T mutation is common in Ph(-) MPD but not critical for transformation to the acute phase of these diseases and that it is generally rare in aggressive leukemias.
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PMID:JAK2 mutation 1849G>T is rare in acute leukemias but can be found in CMML, Philadelphia chromosome-negative CML, and megakaryocytic leukemia. 1603 87

Current diagnostic issues in chronic myeloproliferative disorders (MPDs) include the differentiation of essential thrombocythemia (ET) from its mimics: early (prefibrotic) stages of chronic idiopathic myelofibrosis (CIMF) and early polycythemia vera (PV), both of which can be associated with thrombocytosis. Applying a systematic evaluation of bone marrow histopathology, in accordance with the current World Health Organization (WHO) classification system, it is possible to identify cases of true ET as opposed to false ET, usually early-stage CIMF accompanied by an excess of platelets. This distinction is important because the frequency of complications such as progression to overt myelofibrosis, blastic crisis, and overall prognosis are significantly different in the two conditions. The diagnostic criteria of the Polycythemia Vera Study Group (PVSG) do not adequately define the initial stages of PV, nor do they distinguish PV with thrombocytosis from ET. Differentiation of the two is possible by bone marrow histopathology, which also is highly predictive (96%) in distinguishing PV from secondary polycythemia. In conclusion, bone marrow biopsy is an important diagnostic tool for distinguishing specific subtypes of MPD and should be a mandatory step for entry evaluation and follow-up of patients enrolled in prospective studies and/or clinical trials.
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PMID:Bone marrow histopathology in myeloproliferative disorders--current diagnostic approach. 1621 32

Polycythemia vera (PV) is a clonal disorder of unknown etiology involving a multipotent hematopoietic progenitor cell that is characterized by the accumulation of phenotypically normal red blood cells, white blood cells, and platelets in the absence of a definable cause; extramedullary hematopoiesis, marrow fibrosis, and, in a few patients, transformation to acute leukemia can also occur. First described in 1892, the cause of the disease remains unknown and no potentially curative therapy other than bone marrow transplantation is currently available. It is commonly held that PV is a rare disorder, when in fact with a minimum incidence of 2.6 per 100,000 it is more common than chronic myelogenous leukemia (CML) and is particularly prevalent in persons of Ashkenazi Jewish ancestry. However, the incidence of PV is not as high as that of erythrocytosis from other causes collectively, which poses a problem in differential diagnosis when PV presents as isolated erythrocytosis. Characteristic features of PV are erythropoietin (Epo)-independent in vitro erythroid colony formation, as well as hypersensitivity to many other hematopoietic growth factors. Recently, a remarkable association between PV and a somatic point mutation of the JAK2 tyrosine kinase (JAK2 V617F) was described. Functional assays have revealed that JAK2 V617F is capable of inducing constitutive STAT5-mediated signaling in vitro, as well as erythrocytosis in vivo in mice. These data suggest that the JAK2 V617F mutation participates in the pathogenesis of PV. In current clinical practice, two different clinical approaches have been used to diagnose PV. One approach requires establishing the presence of absolute erythrocytosis by directly determining the red cell mass (RCM). A second approach utilizes a RCM-independent diagnostic algorithm based on the serum Epo level and bone marrow histology. Screening for JAK2 V617F can now be added to both diagnostic algorithms. However, it is very clear that some patients with classical PV lack the JAK2 V617F mutation, while some patients with other chronic myeloproliferative disorders such as idiopathic myelofibrosis (IMF) and essential thrombocytosis (ET) also express the JAK2 V617F mutation. Therefore, by necessity, any discussion of PV must take into consideration these companion myeloproliferative disorders, and since erythrocytosis is the single clinical feature that sets PV apart from IMF and ET, it is clear that the presence of the JAK2 V617F mutation cannot by itself establish a diagnosis of PV. Phlebotomy remains the mainstay of therapy for PV. In addition, both aspirin and cytoreductive therapy have been employed to control thrombocytosis and in the case of the latter, leukocytosis and extramedullary hematopoiesis as well. Despite recent progress in the field, several important issues remain controversial. In this review, we will present the areas of agreement, but also point out where the authors' personal viewpoints differ.
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PMID:Polycythemia vera: scientific advances and current practice. 1621 34

Philadelphia-chromosome-negative chronic myeloproliferative disorders (Ph- CMPDs)--essential thrombocythemia (ET), chronic idiopathic myelofibrosis (CIMF), and polycythemia vera (PV)--may show clinical and morphological similarities, particularly at the early stages. The differential diagnosis of Ph- CMPDs is important due to their different treatment and prognosis. Cytological features of megakaryocytes are considered valuable in this differentiation. To establish an objective measure of megakaryocyte dysplasia in Ph- CMPDs, we performed computer-assisted morphometry of more than 4,000 cells from 20 cases of ET, 10 of CIMF, 10 of PV, and 10 controls. Megakaryocyte sets from three Ph- CMPDs differed significantly in respect to many planimetric parameters, but not a single shape or size parameter could have been used as a discriminative tool between the entities. However, the discriminant function analysis with the simultaneous assessment of 12 planimetric variables allowed for a proper classification of 20 of 20 ET, 10 of 10 PV, and 9 of 10 CIMF cases based solely on the morphometric features of megakaryocytes. Additionally, we identified certain new patterns of megakaryocytes specific for ET, PV, and CIMF, which, although not dominating in one Ph- CMPD, are unlikely to occur in two others. Objective measurements of megakaryocyte sizes and shapes may assist the diagnosis of Ph- CMPDs.
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PMID:Objective, planimetry-based assessment of megakaryocyte histological pictures in Philadelphia-chromosome-negative chronic myeloproliferative disorders: a perspective for a valuable adjunct diagnostic tool. 1622 Feb 96

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. As activation of JAK2 signaling is occurred in other malignancies as well, we have analysed 558 tissues from common human cancers, including colon, breast and lung carcinomas, and 143 acute adulthood leukemias by polymerase chain reaction -- single strand conformation polymorphism analysis. We found three JAK2 mutations in the 113 acute myelogenous leukemias (AMLs) (2.7%), but none in other cancers. The mutations consisted of two V617F mutations and one K607N mutation. None of the AML patients with the JAK2 V617F mutation had a history of previous hematologic disorders. This is the first report on the JAK2 gene mutation in AML, and the data indicated that the JAK2 gene mutation may not only contribute to the development of chronic myeloid disorders, but also to some AMLs.
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PMID:The JAK2 V617F mutation in de novo acute myelogenous leukemias. 1624 55

Recently, the JAK2 V617F mutation has been reported in high proportions of chronic myeloproliferative disorders, including polycythemia vera. To see whether the JAK2 V617F is important in the pathogenesis of lymphoid malignancies, this study analysed the occurrence of the JAK2 V617F mutation in 117 non-Hodgkin lymphomas (NHLs) by a single strand conformation polymorphism assay. However, there was no JAK2 V617F mutation in the NHLs and the data suggest that the JAK2 V617F mutation may not play a role in the development of NHL.
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PMID:JAK2 V617F mutation is uncommon in non-Hodgkin lymphomas. 1632 63

Following the introduction of the WHO classification of chronic myeloproliferative disorders (MPDs), after approximately 5 years, a critical reappraisal appears to be warranted. Retrospective clinico-pathological evaluations conducted in the meantime, as well as the detection of new biomarkers, may aid in testing the validity of these new criteria. Based on a large series of patients with chronic myeloid leukemia (CML), an analysis of bone marrow (BM) features and risk classifications revealed that the fiber content exerted a most important and independent impact on prognosis. This finding was also supported in a prospective randomized study and therefore myelofibrosis should be included in any staging system in CML related to survival. Moreover, it is important to emphasize the dynamics of the disease process in MPDs, especially in polycythemia vera (PV) and chronic idiopathic myelofibrosis (CIMF). Latent-stage PV is difficult to recognize when adhering to the proposed limits for hemoglobin (or red cell mass) without regarding the erythropoietin (EPO) level, endogenous erythroid colonies (EECs) or BM histopathology. Initial PV may firstly present with complications and, when accompanied by a high platelet count, mimics essential thrombocythemia (ET). Consequently, BM morphology and EPO level should be entered as major diagnostic criteria for PV. To document more accurately the progress of disease, a simplified scoring system concerning myelofibrosis has to be included in the histological description of CIMF. The diagnostic guidelines of BM features in ET should be improved because, usually, there is neither a significant proliferation nor left-shifting of the granulo- and erythropoiesis detectable and no relevant increase in reticulin. A comparison of clinical data and BM morphology reveals that biomarkers (EPO, EECs, PRV-1, JAK2) show an overlapping pattern of positivity between the different subtypes of MPDs.
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PMID:A critical reappraisal of the WHO classification of the chronic myeloproliferative disorders. 1639 60


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