Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Karyotypically unrelated clones were observed in nine of 399 newly diagnosed acute leukemia or myelodysplastic syndrome (MDS) patients: two (3.0%) of 66 French-American-British classification (FAB)-M2 patients, five (12.5%) of 40 M5 patients, one (20%) of five chronic myelomonocytic leukemia (CMMoL), patients, one (12.5%) of eight refractory anemia with excess blasts in transformation (RAEBT) patients, and none (0%) of 177 acute lymphoblastic leukemia patients had such clones. Cytogenetically unrelated clones occurred more frequently in FAB-M5 than in the other subtypes of AL or MDS (p less than 0.01). Five (55%) of the nine patients had trisomy 8, two (22%) had partial deletion of the long arm of chromosome 5 and two had (22%) trisomy 11. Patients had short survival times (median 2 months, range 1-26 months) after detection of unrelated clones; eight of the nine failed to respond to chemotherapy. None of our patients had two phenotypically different leukemic cell populations or underwent phenotypic conversion of leukemic cells during the course of the disease. These findings suggest that the unrelated clones may have been derived from the common leukemic clone without microscopic chromosome changes, and that the different chromosome abnormalities of the unrelated clones may represent additional genetic changes in leukemogenesis.
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PMID:Karyotypically unrelated clones in acute leukemias and myelodysplastic syndromes. 235 93

The FMS gene encodes the functional cell surface receptor for colony-stimulating factor 1, the macrophage- and monocyte-specific growth factor. Codons 969 and 301 have been identified as potentially involved in promoting the transforming activity of FMS. Mutations at codon 301 are believed to lead to neoplastic transformation by ligand independence and constitutive tyrosine kinase activity of the receptor. The tyrosine residue at codon 969 has been shown to be involved in a negative regulatory activity, which is disrupted by amino acid substitutions. This study reports on the frequency of point mutations at these codons, in vivo, in human myeloid malignancies and in normal subjects. We studied 110 patients [67 with myelodysplasia (MDS) and 48 with acute myeloblastic leukemia (AML)], 5 patients being studied at the MDS and the later AML stage of the disease. There was a total incidence of 12.7% (14/110) with mutations in codon 969 and 1.8% (2/110) with mutations in codon 301. Two patients had mutations in the AML stage of the disease but not in the preceding MDS and one had a mutation in the MDS stage but not upon transformation of AML. This is consistent with the somatic origin of these mutations. FMS mutations were most prevalent (20%) in chronic myelomonocytic leukemia and AML type M4 (23%), both of which are characterized by monocytic differentiation. One of 51 normal subjects had a constitutional codon 969 mutation, which may represent a marker for predisposition to myeloid malignancy.
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PMID:FMS mutations in myelodysplastic, leukemic, and normal subjects. 240 20

We have developed a RIA for erythrocyte acid glutathione S-transferase (GST), which is immunologically identical to major GSTs from other blood cell components, and measured its serum concentrations in various hematological disorders. In some patients with paroxysmal nocturnal hemoglobinuria, chronic myelomonocytic leukemia, chronic myelocytic leukemia, polycythemia vera and myelofibrosis, the concentrations were high. Very high levels were found in 2 of 3 patients with acute lymphocytic leukemia, while acute myelocytic leukemia exhibited a modest increment. No or little increase was seen in aplastic anemia and myelodysplastic syndrome except chronic myelomonocytic leukemia. It is suggested that the measurement of serum acidic GST may be of use as a clinical marker of increased destruction and/or overproduction of blood cells.
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PMID:Radioimmunoassay for erythrocyte acidic GSH S-transferase. 249 36

T cell subpopulations, defined by monoclonal antibodies (OKT3, OKT4 and OKT8), were assessed on 13 patients with myelodysplasia (MDS). The percentage and numbers of OKT3- and OKT4-positive lymphocytes were significantly lower (p less than 0.025) than in normal controls, whereas those of OKT8 were not. In the group of patients with refractory anemia with excess of blasts (RAEB) and in those with chronic myelomonocytic leukemia, the percentage and absolute numbers of OKT8 lymphocytes were significantly lower (p less than 0.025) than in patients with refractory anemia or with primary acquired sideroblastic anemia, while those of OKT3 and OKT4 did not differ significantly. Quantitative impairment of T cell subpopulations may be part of the myelodysplastic situation as a result of the dyslymphopoiesis, according to the hypothesis that MDS originate from pluripotent stem cells. The decrease of OKT8 in RAEB and chronic myelomonocytic leukemia could be related to the previously shown insufficient erythropoietic activity in these patients.
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PMID:T lymphocyte subpopulations in myelodysplastic syndromes. 250 89

To determine the activity of fenretinide in patients with myelodysplastic syndromes, 15 patients were treated (300 mg/d starting dose, escalated to 400 mg/d) for a 12-week course. No responses were observed in 14 evaluable patients. Exacerbation of thrombocytopenia occurred in one patient with chronic myelomonocytic leukemia, who succumbed to an intracerebral hemorrhage after 3 weeks of treatment. Two patients with long-standing stable sideroblastic anemia experienced interval leukemic progression. In one patient, clinical features of chronic myelomonocytic leukemia appeared, characterized by a striking rise in peripheral monocyte count (0.49 x 10(9)/l to 10.8 x 10(9)/l) and hepatosplenomegaly, which resolved promptly after cessation of treatment. The second patient experienced evolution into acute myelomonocytic leukemia with cytogenetic progression. The drug was well tolerated with no patient having to discontinue treatment because of toxicity. We conclude that fenretinide lacks clinical efficacy in the treatment of myelodysplasia and in some patients may enhance leukemic progression.
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PMID:Phase II trial of fenretinide [N-(4-hydroxyphenyl) retinamide] in myelodysplasia: possible retinoid-induced disease acceleration. 252 91

Restriction fragment length polymorphisms (RFLPs) of the X-chromosome genes hypoxanthine phosphoribosyl transferase (HPRT) and phosphoglycerate kinase (PGK) were studied in 34 female patients with primary myelodysplastic syndromes (MDS). Twelve patients (35%) were heterozygous at the HPRT or PGK loci for BamHI or BglI RFLPs, respectively. In eight patients showing PGK polymorphisms, clonality was determined by X-chromosome inactivation analysis. These included patients from different morphologic subtypes: four with refractory anemia (RA), two with RA and ring sideroblasts (RARS), one patient with RA with excess of blasts (RAEB), and one with chronic myelomonocytic leukemia (CMML). A monoclonal pattern of X-chromosome inactivation was observed in seven cases. In a further case characterized by bone marrow hypoplasia, peripheral blood (PB) leukocytes were polyclonal in origin. Following low-dose cytarabine therapy, reversion to polyclonal hematopoiesis was observed in a case of RAEB indicating the presence of residual normal hematopoietic stem cells with the capacity for marrow reconstitution. The clonal relation of lymphoid and granulocyte/monocyte lineages was studied directly in two cases of CMML exhibiting somatic mutations of N-ras or Ki-ras oncogenes. By selective oligonucleotide hybridization to ras gene sequences amplified in vitro by the polymerase chain reaction, a mutated ras allele was demonstrated in PB granulocytes, monocytes, and B and T lymphocytes of both patients. We conclude that MDS arise from a multipotent hematopoietic stem cell with the potential for myeloid and lymphoid differentiation.
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PMID:Clonal analysis of myelodysplastic syndromes: evidence of multipotent stem cell origin. 256 24

Systematic clinical and laboratory observations of 64 cases of myelodysplastic syndrome (MDS) were made. The results showed that malignant clone already exists in the bone marrow of patients with MDS. Eighteen cases of them have transformed into AML. The rates of transforming into AML in RAEB, RAEB-T and CMML were markedly higher than that in RA. The courses of MDS which transformed into AML from the various types were different. The transformation in RA was obviously longer than those in RAEB and RAEB-T. Two cases transformed into myelofibrosis. Diagnosis of CMML according to the FAB classification criteria revealed that it has two forms. One shows only increase of mature monocytes and it has no relation with the types of acute leukemia to be transformed. It is considered as a reactive monocytosis. The other form, in addition to increase of mature monocytes, also has increase of a few monoblasts and promonocytes. These are considered as true CMML and usually quickly developed into M4 or M5 which are related with monocytes.
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PMID:[A clinical study on myelodysplastic syndrome. Report of 64 cases]. 259 Dec 61

A series of 116 patients with MDS consisted of 74 cases of RA, 10 cases of RARS, 14 cases of RAEB, 9 cases of RAEB-T and 9 cases of CMML, were studied on the quantity and morphological abnormalities of megakaryocytes in relation to over all survival and leukemic change. The amount of megakaryocytes was graded into four groups; marked hypoplasia (O), moderate hypoplasia (L), normoplasia (N) and hyperplasia (H), RA cases showed heterogeneous pattern; containing 14 cases (18.9%) of group (O), 18 cases (24.3%) of group (L), 31 cases (41.9%) of group (N) and 11 cases (14.9%) of group (H). RARS, RAEB, RAEB-T and CMML cases were classified into group (N) or group (H). The heterogeneous pattern of RA did not relate to leukemic change, but over all survival tended to be shorter in group (N) cases. A significant number of young female cases of RA were involved in group (O). Morphological abnormalities of MDS megakaryocytes were classified into five types; I, mononuclear micromegakaryocytes, II, binuclear micromegakaryocytes, III, mononuclear small megakaryocytes, IV, multiseparated-nuclear megakaryocytes and V, megakaryocytes with bizzare nuclei. RAEB and RAEB-T cases uniformly showed marked dysmegakaryopoiesis ranging from type I to V. whereas RA, RARS and CMML cases showed mild dysmegakaryopoiesis. Only five cases (6.4%) of RA cases had type I micromegakaryocytes. Eight RA cases with type I on diagnosis or obtaining it during the clinical course tended to develop acute myeloid leukemia (5 cases) or to transform to RAEB sooner or later. In two cases of RAEB in which hematological improvement was obtained with low dose cytosine arabinoside regimen, disappearance of type I micromegakaryocytes was noted. A female case with 5q-anomaly surviving more than 10 years showed marked megakaryocyte hyperplasia and almost exclusively type III and IV megakaryocytes. These findings indicated that pattern of dysmegakaryopoiesis, especially appearance of type I, was closely related to leukemic change in MDS. Thus quantitative and qualitative evaluations of MDS megakaryocytopoiesis seemed important to understand the further heterogeneity of pathophysiology in MDS subtypes.
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PMID:[Study on pathophysiology of the myelodysplastic syndromes (MDS)--pattern of dysmegakaryopoiesis related to leukemic transformation]. 259 45

A retrospective clinical review of 41 patients with chronic myelomonocytic leukemia revealed a median age of 66 years and a male:female ratio of 2.4:1. The disease was preceded by a myelodysplastic syndrome of a different subtype in 24% of the patients and transformed into acute leukemia in 24%. Splenomegaly was present in 54% of the patients and reached massive proportions in 24%. Chromosomal abnormalities occurred in 34% of those studied, most commonly in the younger age group; the most frequent were trisomy 8, monosomy 7, and deletions involving the long arms of chromosomes 20 and X. Polyclonal hypergammaglobulinemia was detected in 47% of the patients in whom serum protein electrophoresis was done. The median survival was 3 years. With use of univariate analysis, the statistically significant prognostic determinants were hemoglobin level, the "modified Bournemouth score," and bone marrow blast cell percentage. When these factors were subjected to a multivariate analysis, only bone marrow blast cell percentage was an independent prognostic determinant. Orally administered hydroxyurea controlled leukocytosis and splenomegaly in some patients without affecting the overall prognosis.
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PMID:Chronic myelomonocytic leukemia: natural history and prognostic determinants. 259 15

Clinical features, prognosis and factors influencing survival, as well as long-term evolution of the disease were analyzed in 130 patients with myelodysplastic syndromes (MDS) with particular reference to the refractory anemia with excess of blasts (RAEB). Survival of patients with 3 FAB subtypes, RAEB, RAEB in transformation (RAEB-T) and chronic myelomonocytic leukemia (CMMoL) showing excess blasts was uniformly poor relative to primary acquired refractory anemia (PARA) and primary acquired sideroblastic anemia (PASA). The degree of cytopenias, karyotypic abnormalities, bone marrow cellularity, transition to acute leukemia were not reliable prognostic parameters for discrimination of RAEB with poor or good prognosis. Disease transition was frequently observed in our MDS patient population, at an overall incidence of 37.7%. Transition of PARA to RAEB occurred after a prolonged course in some patients.
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PMID:Clinical aspects of the myelodysplastic syndromes (MDS) with special reference to refractory anemia with excess of blasts (RAEB). 261 56


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