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Query: UMLS:C0026986 (myelodysplastic syndrome)
14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is lack of information about the relative prevalence of haematological disorders in Yemen and other Middle East countries. The aim of this study was to evaluate the pattern of haematological diseases diagnosed by bone marrow examination in Yemen considering the limited diagnostic facilities. At the referral haematology centre in Yemen, between November 1999 and November 2005, 785 patients >14 years old were evaluated by bone marrow examination. Relevant investigations were performed when needed. A total of 627 patients had haematological disorders other than lymphoma, and their data were analysed. There were 273 females and 354 males. A total of 159 patients had Acute myeloid leukaemia, 75 had acute lymphocytic leukaemia, 87 had chronic myeloid leukaemia, 36 chronic lymphocytic leukaemia, eight had multiple myeloma, 13 myelodysplastic syndromes, seven myelofibrosis, seven polycythaemia vera, three primary thrombocythaemia, two hairy cell leukaemia, two metastases, 36 aplastic anaemia, 29 immune thrombocytopenic purpura (ITP), nine autoimmune haemolytic anaemia, three pernicious anaemia, 65 iron deficiency anaemia, 57 megaloblastic anaemia and malaria, 18 mixed deficiencies, and 11 patients had visceral leishmaniasis. Sex- and age-related distribution of the various disorders was also presented. In conclusion, the leukaemias were the most frequently encountered diagnosis followed by iron deficiency anaemia, megaloblastic anaemia and malaria, aplastic anaemia and ITP respectively. The other haematological disorders were less common. These findings are comparable with that seen in other developing and developed countries.
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PMID:Pattern of haematological diseases diagnosed by bone marrow examination in Yemen: a developing country experience. 1710 90

Defined by isolated del 5q and no excess of marrow blasts, the "5q- syndrome" is a specific type of myelodysplastic syndrome (MDS) with particular characteristics, including severe anemia, frequent thrombocytosis, typical dysmegakaryopoiesis and favorable outcome. Its pathogenesis remains uncertain, in particular the role of inactivation of gene(s) situated in 5q. It should be differentiated from other MDS with del 5q having an excess of marrow blasts and/or additional cytogenetic abnormalities, which carry a poor prognosis. Until the advent of lenalidomide, repeated RBC transfusions were generally the only treatment of the 5q- syndrome, which was resistant to other therapeutic approaches. Lenalidomide can lead to RBC transfusion independence in at least two thirds of cases of the 5q- syndrome, two thirds of those responses persisting after 2 years of treatment. Importantly, not only reversal of anemia but also frequent complete pathological and cytogenetic responses are obtained. Grade 3 or 4 neutropenia and thrombocytopenia, especially during the first 6 to 8 weeks of treatment, are the major side effect of lenalidomide, justifying close monitoring of blood counts and regular patient visits. Preliminary results suggest that lenalidomide is also very active in MDS with del 5q other than the 5q-syndrome. Although its mechanism of action remains uncertain, lenalidomide appears to target specifically the del 5q clone. By doing this, lenalidomide may have an effect on disease course and survival, which is currently being assessed in clinical trials.
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PMID:Treatment of the 5q- syndrome. 1712 60

JAK2V617F, a somatic gain-of-function mutation involving the JAK2 tyrosine kinase gene, occurs in nearly all patients with polycythemia vera (PV) but also in a variable proportion of patients with other myeloid disorders; mutational frequency is estimated at approximately 50% in both essential thrombocythemia (ET) and myelofibrosis (MF), up to 20% in certain subcategories of atypical myeloproliferative disorder (atypical MPD), less than 3% in de novo myelodysplastic syndrome (MDS) or acute myeloid leukemia, and 0% in chronic myeloid leukemia (CML). Accordingly, there is now molecular justification for grouping PV, ET, and MF together in a distinct MPD category (i.e., classic, BCR-ABL(-) MPD) that is separate from chronic myeloid leukemia (CML), MDS, and atypical MPD. To date, JAK2V617F has not been described in patients with reactive myeloproliferation, lymphoid disorders, or solid tumor. Therefore, the presence of JAK2V617F strongly suggests an underlying MPD and it is therefore reasonable to consider JAK2V617F-based laboratory tests for the evaluation of polycythemia, primary thrombocytosis, unexplained leukocytosis, bone marrow fibrosis, or abdominal vein thrombosis. Current information on disease-specific prognostic relevance of JAK2V617F is inconclusive and confounded by inter-study differences in the performance of mutation screening assays. Regardless, the discovery of JAK2V617F has reinforced the pathogenetic contribution of JAK-STAT signaling in MPD and identifies JAK2 as a valid drug target.
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PMID:Classification, diagnosis and management of myeloproliferative disorders in the JAK2V617F era. 1712 67

The bone marrow criteria defined by the World Health Organization (WHO) are based on characteristic increase and clustering of morphologically abnormal enlarged megakaryocytes as a pathognomonic clue to describe three distinct phenotypic entities of myeloproliferative disorders (MPDs): (1) essential thrombocythemia (ET), (2) early and overt polycythemia vera (PV) and (3) prefibrotic, early fibrotic, and fibrotic chronic idiopathic myelofibrosis (CIMF-0, 1, 2 and 3). Based on established WHO bone marrow features, and the use of new molecular and laboratory markers including JAK2(V617F) mutation, endogenous erythroid colony (EEC) formation and serum erythropoietin (EPO), we present updated European clinical, molecular and pathological (ECMP) criteria for the differential diagnosis of true ET, PV and CIMF. As compared to the WHO bone marrow features, each of the laboratory and molecular markers are not sensitive enough for the diagnosis and classification of the three prefibrotic MPDs. The proposed WHO/ECMP criteria reduce the platelet count to the upper limit of normal (>400x10(9)l(-1)) as inclusion criterion for the diagnosis of thrombocythemia in true ET, early stages of PV and prefibrotic CIMF. The combined use of WHO and ECMP criteria differentiate PV from congenital and acquired erythrocytosis, true ET from reactive thrombocytosis and separates true ET from CIMF-0/1 mimicking ET. Only half of the patients with true ET and CIMF carry the JAK2(V617F) mutation (sensitivity 50%). Early PV mimicking ET is featured by the presence of JAK2(V617F) mutation, EEC, low serum EPO levels, normal hematocrit, and increased bone marrow cellularity due to increased erythropoiesis ("forme fruste" PV) when WHO/ECMP criteria are applied. The combination of JAK2(V617F) PCR test and increased hematocrit is diagnostic for PV (sensitivity 95%, specificity 100%). The degree of JAK2(V617F) positivity of granulocytes is related to disease stage: heterozygous in true ET and early PV and mixed hetero/homozygous to homozygous in overt and advanced PV and CIMF. Bone marrow histology assessment should remain the gold standard criterion for the diagnosis and staging of the MPDs true ET, PV and CIMF and its differentiation from primary or secondary erythrocytosis, reactive thrombocytosis and thrombocythemias associated with atypical MPD, myelodysplastic syndromes, and chronic myeloid leukemia,. The proposed WHO/ECMP criteria allow a cross talk between clinicians, pathologists and scientists to much better characterize the nature and natural history of each of the WHO/CMP defined early and overt MPDs.
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PMID:WHO bone marrow features and European clinical, molecular, and pathological (ECMP) criteria for the diagnosis of myeloproliferative disorders. 1736 53

We observed increased ferritin levels in newly diagnosed MDS-RARS patients without transfusional iron-overload. Hence, we hypothesized RARS patients may harbor hemochromatosis-related mutations, which could contribute to the pathophysiology of this myelodysplastic syndromes (MDS) subset. We studied a cohort of 140 MDS patients: 42 with RARS, 10 with increased ringed sideroblasts, and 96 with other forms of MDS (43 RA, 27 RAEB, 17 RAEB-T, 8 MDS/MPD, 1 CMML). Patients were genotyped using restriction fragment length polymorphism, designed to detect C282Y and H63D mutations of the HFE gene. We found significantly higher frequency of heterozygosity for C282Y mutation in RARS patients compared with a large control population of matched race individuals (21 vs. 9.8% in controls, P = 0.03); H63D genotype was not significantly increased. Frequency of HFE variation in other MDS subtypes failed to differ significantly from controls. Within this group, we included patients with a rare form of MDS, provisionally subclassified by WHO as RARS with thrombocytosis (RARSt). 10/14 RARSt patients were carriers of either C282Y or H63D allele significantly increased compared with the combined prevalence in a healthy population (71 vs. 33%, P < 0.01). We found expected distribution of mutant HFE alleles in patients with other forms of MDS (9.1 vs. 9.8%, P = 0.82). Increased prevalence of HFE gene mutations is not a generalized feature of MDS, but some subgroups of MDS, especially those characterized by excessive accumulation of ringed sideroblasts, exhibit C282Y mutations at a higher frequency than in other forms of MDS and healthy controls.
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PMID:Hemochromatosis-associated gene mutations in patients with myelodysplastic syndromes with refractory anemia with ringed sideroblasts. 1765 85

We report a case of acute leukemia with an isolated isochromosome 17q karyotypic abnormality, which may be transformed from myeloproliferative disease (MPD)/myelodysplastic syndrome (MDS). A 69-year-old male patient with 27% of blasts in the peripheral blood underwent hematological examinations including cytochemical staining of cells such as myeloperoxydase (MPO), surface marker study on blasts, chromosomal test and bcr-abl mRNA analysis. The cytological and molecular findings (MPO-positive, myeloid marker CD13 expression (67.3%) and megakaryocytic marker CD41 expression (24.8%)) indicated that the blasts were consistent with myeloid leukemic cells partially committed to megakaryocytes. He was diagnosed as having leukemic transformation from MPD/MDS based on history of leukocytosis and thrombocytosis, isolated i(17q), bcr-abl negative, hepatosplenomegaly, increased eosinophil/basophil count and cytologic dysplasia. Positivity of BMI-1 in CD34+ blasts was 25.8% at the diagnosis and anti-leukemic drugs including anthracyclines were effective for his disease control during 6 months. However, the CD34+ cells turned out to highly express BMI-1 (83.1%), and leukemic cells started to increase progressively following which the leukemic cells failed to respond efficiently to any anti-leukemic drugs. Thus, expression of BMI-1 was well correlated with the disease progression, growth ability of blasts and resistance to anti-cancer drugs, indicating that BMI-1 positivity in CD34+blasts is an excellent molecular marker for disease progression and prognosis in such patients.
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PMID:[Exacerbation of acute leukemia bearing isolated i(17q) along with proliferation of blasts with high BMI-1 expression]. 1786 4

An increased platelet number in blood depends on a limited spectrum of causes, which aren't always simple to identify. Secondary thrombocytosis is a reactive process in relation with acute or chronic inflammatory diseases, or asplenia. The infrequent inherited thrombocytoses disorders are suspected when similar cases are observed in the same family. However, the most frequent causes of chronic thrombocytosis in adults are the so-called chronic myeloproliferative syndromes (chronic myelocytic leukaemia, polycythemia vera, primary myelofibrosis, essential thrombocytemia), and to a lesser extent, myelodysplastic syndromes. In the course of these disorders, thrombocytosis is often the first recognized abnormality. Chronic myelocytic leukaemia is easily diagnosed owing to the presence of either the Philadelphia chromosome or the BCR-ABL fusion gene product. The next step still relies upon a distinction according to the PVSG or the WHO criteria of Polycythemia Vera (PV) and Idiopathic myelo fibrosis (IMF) to finally confirm genuine Essential Thrombocythemia (ET). The recent description of the V617F mutation of JAK2 in 90% of PV patients, 43 to 67% with IMF and 50% of ET diagnosed according to either the PVSG or the WHO criteria is a definite characteristic of clonality now accessible in haematology practice. However, this mutation is neither specific nor constant in any of the Philadelphia negative myeloproliferative disorders, which outlines the importance of the WHO criteria of megakaryocytic abnormalities on bone marrow biopsy as the hallmark of Ph negative MPDs. The exclusion of PV and of IMF, including pre fibrotic and early fibrotic forms is still required for the diagnosis of "true" ET. Disease stratification and treatment strategy are targeted on the evaluation and prevention of vascular complications. Acute leukaemia or myelodysplasia, and other clonal progressions like myelofibrotic transformation, are infrequent and delayed events. However, according to the present data, the risk of fibrotic progression or of leukaemic transformation is not related to the mutation status of ET patients.
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PMID:[Essential thrombocythemia. Contribution of the V617F JAK2 mutation to the pathophysiology, diagnosis and outcome]. 1807 52

Defined by isolated del 5q and no excess of marrow blasts, the '5q- syndrome' is a specific type of myelodysplastic syndrome (MDS) with particular characteristics, including severe anaemia, frequent thrombocytosis, typical dysmegakaryopoiesis and favourable outcome. Its pathogenesis remains uncertain, particularly regarding the role of the inactivation of gene(s) situated in 5q. Until the advent of lenalidomide, repeated red blood cell (RBC) transfusions were generally the only treatment for 5q- syndrome, which was resistant to other therapeutic approaches. Lenalidomide can lead to RBC transfusion independence in at least two-thirds of cases of 5q- syndrome, and about one half of those responses are maintained after 2 years of treatment. Importantly, frequent complete pathological and cytogenetic responses are also obtained. Grade 3 or 4 neutropenia and thrombocytopenia, especially during the first 6-8 weeks of treatment, are the major side effects of lenalidomide, justifying close clinical and blood counts monitoring. Preliminary results suggest that lenalidomide is also active in MDS with del 5q other than the 5q- syndrome. The mechanisms of action of lenalidomide, although uncertain, appear to include targeting of the del 5q clone. Therefore, lenalidomide may have an effect on disease course and survival, which is currently being assessed in clinical trials.
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PMID:The role of lenalidomide in the management of myelodysplasia with del 5q. 1851 Jun 84

Abnormal nuclear megakaryocytic staining for phospho-STAT5 (pSTAT5) correlates with JAK2 V617F mutational status in non-chronic myelogenous leukemia chronic myeloproliferative disorders. However, a proportion of wild-type JAK2 non-chronic myelogenous leukemia chronic myeloproliferative disorders cases also demonstrate this abnormal pSTAT5 expression pattern. We report a patient with a JAK2 V617F-negative myeloproliferative/myelodysplastic syndrome who had abnormal megakaryocytic pSTAT5 expression and a MPL W515L mutation. The patient was a 71-year-old man with anemia and thrombocythemia on laboratory examination. His peripheral blood smear demonstrated occasional dysplastic neutrophils. Bone marrow biopsy revealed hypercellular marrow with features consistent with myeloproliferative/myelodysplastic syndrome. Immunohistochemistry for pSTAT5 showed abnormal nuclear megakaryocyte positivity. Cytogenetic analysis revealed a normal karyotype, fluorescence in situ hybridization for BCR-ABL was negative, and JAK2 genotyping demonstrated wild-type JAK2. However, MPL genotyping showed a MPL W515L mutation. Abnormal nuclear megakaryocytic staining for pSTAT5 expression, previously associated with the JAK2 V617F mutation, is also associated with MPL W515L, likely reflecting activation of the JAK-STAT signaling pathway.
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PMID:Phospho-STAT5 expression pattern with the MPL W515L mutation is similar to that seen in chronic myeloproliferative disorders with JAK2 V617F. 1847 30

An 18-year-old female alpaca was presented to the Colorado State University Veterinary Teaching Hospital for chronic ill thrift over a 1-year period. Six weeks previously, an infected left mandibular cheek tooth was removed by oral extraction. On physical examination the patient was cachectic, lethargic, and weak. Abnormalities on the CBC included neutropenia, thrombocytosis, and severe nonregenerative, macrocytic, hypochromic anemia. Dysplastic nucleated erythrocytes and micromegakaryocytes were observed on the peripheral blood smear. Neutrophils, bands, and metamyelocytes appeared markedly toxic. Numerous blasts containing variable numbers of fine azurophilic granules were also observed. Based on their morphology, the cells were interpreted to be progranulocytes and myeloblasts, and a presumptive diagnosis of acute myeloid leukemia (AML) was made. The blast cells accounted for 60% of the nucleated cell population on bone marrow aspirates, further supporting a diagnosis of AML with multilineage dysplasia. Post mortem examination showed infiltration of the neoplastic cells into spleen, liver, kidney, and lymph nodes. Based on histologic findings, the morphologic diagnoses were disseminated myeloid neoplasia, chronic regionally extensive tooth root abscess, and membranous glomerulonephritis. The neoplastic cells were CD172a-positive on flow cytometry, chloroacetate esterase-positive by cytochemistry, and myeloperoxidase-positive by immunohistochemistry, confirming myeloid origin. To our knowledge, this is the first case of AML with multilineage dysplasia in an alpaca, with only one other case of myelodysplasia described previously in this species.
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PMID:Acute myeloid leukemia with multilineage dysplasia in an alpaca. 1876 21

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