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)

Myelodysplasia is an increasingly recognized complication of polycythemia vera (PCV) which often precedes leukemic transformation. This paper describes two patients with aggressive chronic myelomonocytic leukemia, previously undescribed as a complication of PCV. Both patients presented with rapidly increasing splenomegaly which was resistant to treatment with hydroxyurea and external beam irradiation. Splenectomy precipitated fatal hepatic failure in one patient. The other died shortly after transformation to acute myelomonocytic leukemia (FAB M4 classification). Pathology of the bone marrow, spleen, and liver was remarkable for extensive infiltration by dysplastic myeloid elements. Survival was short, only 4-6 months from diagnosis. The unique characteristics in these patients were: (i) prior history of PCV; (ii) rapidly increasing splenomegaly resistant to standard therapy; (iii) absence of overt marrow fibrosis; (iv) hypercellularity (greater than or equal to 90% cellular) of the bone marrow with dysplasia in the myeloid, erythroid, and megakaryocytic cell lines; (v) peripheral monocytosis greater than 1 x 10(9); and (vi) extensive infiltration of the spleen and liver by dysplastic myeloid cells. In addition, the patient who subsequently developed acute leukemia had been treated with hydroxyurea under the PVSG-08 protocol, providing further evidence of the potential leukemogenic effects of this agent.
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PMID:Chronic myelomonocytic leukemia transformation in polycythemia vera. 207 46

Morphological features of megakaryocytes were studied in 31 patients with myelodysplastic syndrome. Mean nuclear size (N), mean cytoplasmic size (C) and mean N/C ratio were 586 +/- 105 mu 2, 1,391 +/- 327 mu 2 and 0.42 +/- 0.04, respectively. Cell sizes were found to be reduced in 12 patients compared to control subjects. Atypical megakaryocytes were frequently found in patients with RAEB and micromegakaryocytes were also often found in patients with CMML. Mean platelet volume was 0.9 +/- 1.6 fl and the giant platelets were seen in one patient with CMML. In the patients with presence of more than 10% of atypical megakaryocytes, template Ivy bleeding time prolonged and epinephrine- and collagen-induced aggregation decreased. We believe that reduction of megakaryocytes' size and appearance of micromegakryocytes would be helpful in diagnosis of MDS.
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PMID:[Morphological analysis of the megakaryocytes in myelodysplastic syndrome]. 208 33

We performed Southern blot analysis of the p53 gene in 62 patients (37 de novo myelodysplastic syndromes (MDS), of which 10 were studied after progression to acute myeloid leukemia (AML); 14 MDS secondary to chemo or radiotherapy; 11 de novo AML). Thirteen of the 56 patients studied cytogenetically had monosomy for the short arm of chromosome 17 and, in another patient who had secondary MDS, a translocation involving a breakpoint in 17p13 where the p53 gene was mapped was found. This patient was the only individual in whom a rearrangement of p53 DNA was seen. Sixteen of the 62 patients were studied by Northern analysis, and reduced or undetectable 2.8 kb p53 transcript was found in 6 of them, who had predominantly monosomy for 17p or chronic myelomonocytic leukemia. Rearrangements of the 53 gene, identifiable by Southern analysis, are a rare finding in patients with MDS and AML, even in those with monosomy for 17p, but reduced expression of the p53 gene is relatively common. We are currently trying to detect point mutations of the p53 gene by PCR technology especially in patients with monosomy for 17p.
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PMID:Rearrangement and expression of the p53 gene in myelodysplastic syndrome and acute myeloid leukemia. 209 8

Eight patients with myelodysplastic syndrome (MDS; RA = 1, RAEB = 2, RAEB-t = 4, CMML = 1) received three cycles of recombinant gamma-IFN administered in 2-week intervals, each consisting of a 14-day period of subcutaneous injections at a daily dose of 0.1 mg/m2. Neither a complete nor a partial remission could be obtained. There was only one definite improvement consisting in a rise of hemoglobin level from 7 to more than 12 g/dl. Two minor improvements were due to a slight rise of platelet counts. Three patients developed acute leukemia under treatment with gamma-IFN. Our data suggest that gamma-IFN administered according to the treatment schedule as used in our trial has only a minimal beneficial effect in patients with MDS.
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PMID:Gamma-interferon in myelodysplastic syndromes: a pilot study. 211 96

We studied granulocyte-macrophage (GM) colony formation in chronic myelomonocytic leukemia (CMML, 6 cases), as compared with that in myelodysplastic syndromes (MDS, 6 cases) and myeloproliferative disorders (MPD, 12 cases). GM colony formation of bone marrow cells by colony-stimulating factor (CSF) was normal in CMML and MPD patients, but was decreased in MDS patients. Circulating granulocyte-macrophage progenitors (CFU-GM) were detected in CMML and MPD patients, but not in MDS patients. GM colony formation without CSF was observed in CMML patients, but not in MDS or MPD patients. These endogenous colonies decreased markedly after adherent cell (AdC) depletion, but AdC did not form endogenous colonies in sufficient numbers to explain their marked decrease after AdC depletion. In CMML patients, the numbers of circulating CFU-GM and endogenous colonies correlated with leukocyte and monocyte counts, respectively. The cellular composition of GM colonies was normal in MDS and MPD patients, whereas granulocytic colonies predominated in all CMML patients but one. The CSF-producing capacity of peripheral blood cells was also studied and was found to be increased in CMML patients. This capacity was markedly decreased by AdC depletion; and AdC could produce CSF only in CMML patients. CSF produced by CMML patients supported granulocytic colonies to a greater extent than CSF produced by MDS or MPD patients. These results suggest that enhanced granulopoiesis in CMML patients is closely associated with the possible hyperproduction of granulocytic CSF by their adherent monocytes.
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PMID:Characteristics of granulocyte-macrophage colony formation in chronic myelomonocytic leukemia: a comparative study with other myelodysplastic and myeloproliferative disorders. 211 95

Myelodysplastic syndrome (MDS) is frequently associated with monocytosis in the blood and myelomonocytic dysplasia in the bone marrow. In two groups of patients with MDS, all subtypes excluding CMML, the authors demonstrated that monocytosis was present in 15% of the patients in group I according to the haemogram at the time when the diagnosis was established and in 19% in group II where it was required that at least in half the haemograms throughout the course of the disease there were more than 10% monocytes. No difference was found in the prognosis of patients with monocytosis, as compared with patients with monocytopenia as regards the life span and frequency of transformation into AL. The cytogenetic and cultivation findings did not differ either. In some instances, in particular in patients with RA and RAS significant monocytosis was not associated with the expected proliferation of monocytoid cells in bone marrow. The authors assume that proliferation and differentiation of germ cells in the monocytic series is easier than in the granulocytic series and that monocytosis can be considered a manifestation of substituted neutropenia. The work indicates the difficulties associated with the differential diagnosis of RA, RAS and RAEB with monocytosis, MDS with a dominating change of the type of myelomonocytic dysplasia and CMML proper.
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PMID:[Monocytosis and myelomonocytic dysplasia in myelodysplastic syndrome]. 213 57

We report here a rare transformation from refractory anemia with ring sideroblasts (RARS) to chronic myelomonocytic leukemia (CMML). A rare karyotype, inv (12), was also seen at the phase of CMML. A 76-year-old female consulted a physician because of hoarseness in June, 1983. An anemia was found and blood transfusions were made. In August, 1983, she was referred and admitted to Tsukuba University Hospital for a further examination of anemia. A diagnosis of MDS (RARS) was made by hematological examinations, and pyridoxamine was administered from September, 1983. The monocyte counts in the peripheral blood increased above 1,000/microliters continuously from June, 1985, and an exacerbation of anemia was also seen. At the second admission to our hospital in August, 1988, the diagnostic criteria for CMML by the FAB co-operative group was fulfilled. At that time, chromosomal analysis revealed an abnormal karyotype; 46XY, inv (12) (p13.3 q15). Even at the phase of CMML, ringed sideroblasts were also seen in 2.2% of nucleated cell count in the bone marrow. To our knowledge, only 12 cases have been reported as transformation from another type of MDS to CMML. The present case is thought to be a rare case of transformation of MDS. On the other hand, 8 cases with inv (12) associated with malignant hematological disorders have been reported previously. Four of the above 8 cases were MDS. A relationship between development of MDS and inv (12) was suggested.
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PMID:[Chronic myelomonocytic leukemia transformed from refractory anemia with ring sideroblasts with a rare abnormal chromosome, inv (12)]. 217 2

As part of a multicenter trial 12 patients with myelodysplastic syndromes (MDS) were treated with 14-day-cycles of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; 250 micrograms/m2 day s.c.). In addition, all patients received 20 mg/m2/day s.c. cytosine-arabinoside (Ara-C) 12 h after GM-CSF except for patients suffering from refractory anemia (RA) according to FAB classification. Courses were repeated after 4 weeks. In 11 evaluable patients, results according to FAB-classified MDS were as follows: RA, 1/2 response (R), 1/2 stable disease (SD); RAEB, 2/3 R, 1/3 SD; RAEB-T, 1/6 CR, 1/6 PR, 2/6 R, 2/6 progression; CMML, 1/2 SD. In 2 patients with RAEB-T, overt acute myeloid leukemia was observed 2 and 10 weeks after initiation of treatment. With few exceptions, treatment resulted in a prompt increase in granulocytes and eosinophiles. This was associated with improvement of infectious complications. Increases in red cells and platelets occurred variably and was apparently associated with responses of the underlying disease. Dose limiting side effects consisted of fever, severe fatigue and dolent local reactions at the site of GM-CSF injection. In addition, nausea and diarrhoea occurred frequently. Less often, respiratory and cardiovascular side effects were encountered. In summary, GM-CSF +/- Ara-C in MDS results in objective remission with manageable toxicity. Conceivably, this regimen will serve as a base for future treatment strategies against MDS.
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PMID:Recombinant human granulocyte-macrophage colony-stimulating factor and low-dose cytosine-arabinoside in the treatment of patients with myelodysplastic syndromes. A phase II study. 218 22

We analyzed the prognostic value of clinical, hematologic and bone marrow (BM) histologic findings at presentation in 94 patients with myelodysplastic syndromes (MDS) (28 RA; 2 RARS; 34 RAEB; 6 CMML; 24 RAEB-t). With survival as the dependent variable, stepwise multivariate analysis indicated as the prognostically most important factors among the MDS taken as a whole: latency from the first symptoms to diagnosis, age, and percentage of BM blasts. In each main MDS group the most unfavorable initial characteristics were: 1) low Hb, no macro-megaloblastosis, male sex for RA/RARS; 2) low Hb and low platelet levels for RAEB/CMML; 3) granuloblastic hyperplasia and high BM blastosis for RAEB-t. Of the BM histologic parameters, only the percentage of blasts had significant prognostic value. Histologic assessment of BM blastosis, however, did not differ statistically from that based on cytologic examination of BM smears, so that marrow histology seemed not essential for initial prognostic assessment in MDS patients. The finding of abnormal localization of immature precursors (ALIP) in BM biopsies was associated with a negative trend without reaching statistical significance. Using four objective parameters of proven significance (age, Hb, platelets, and BM blasts) we devised a staging system of immediate clinical utility for prognostic stratification and risk-adapted therapeutic choices.
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PMID:Risk assessment in myelodysplastic syndromes: value of clinical, hematologic and bone marrow histologic findings at presentation. 220 26

We studied the expression of IL 6 gene in 49 patients, including 21 chronic myelomonocytic leukemias (CML), 9 other myelodysplastic syndromes (MDS), 18 acute myeloid leukemias (11 M2 or M3 and 7 M4 or M5) and 1 case of acute biphenotypic lymphoid monocytic leukemia. IL 6 was found expressed only in the latter patient and in one patient with M5 acute myeloid leukemia. DNA analysis by Southern blot revealed no rearrangement in these 2 patients and in 10 of the other patients who showed no IL 6 expression. These results do not support an autocrine role for IL 6 in CMML or in other MDS. In acute myeloid leukemias, if expressed by leukemic cells, IL 6 seems to be restricted to cases with a monocytic component, although the number of patients was too small to draw any definite conclusion.
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PMID:Expression of the interleukin 6 gene in acute myeloid leukemia and myelodysplastic syndromes: a report on 49 cases. 221


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