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

The prognostic value of marrow chromosome studies was examined in 112 "preleukemic" patients followed for at least one year or until death. Based on recent definitions, 49 patients were classified as myeloproliferative disorders (MPD) (polycythemia vera, myelofibrosis, undifferentiated myeloproliferative disorder, essential thrombocythemia), and 58 as cytopenic states (refractory anemia, pancytopenia). In each group, approximately one-third had a chromosomally-abnormal clone. For MPD, this had little predictive value, but in the cytopenias, 77% with a cytogenetic abnormality developed leukemia versus 39% without. Twelve cytopenic patients had multiple alterations involving more than 2 chromosomes and 11 died within 6 months, 9 with leukemia. Such patients may warrant consideration for aggressive chemotherapy before the appearance of clinical leukemia. Banding studies did not reveal any specific chromosome abnormalities consistently associated with these various preleukemic disorders, or with progression to leukemia, but nonrandom alterations were noted involving chromosomes 1, 5, 7-9, and 20 in the MPD group, and chromosomes 6 and 16 in the cytopenic patients. Correlation of these data with other reports indicates that certain cytogenetic abnormalities involving specific segments of the human genome confer a selective growth advantage on hemic clones which may present clinically as either preleukemia or leukemia.
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PMID:Chromosome studies in preleukemic states. IV. Myeloproliferative versus cytopenic disorders. 71 5

Patients with myeloproliferative disorders were prospectively studied by in vitro agar-gel marrow culture technics to evaluate factors involved in the evolution of abnormal granulopoiesis. Marrow granulocytic colony-forming capacity was determined in 78 patients with chronic myeloid leukemia, subacute myeloid leukemia, preleukemia, Di Guglielmo's syndrome, polycythemia vera or essential thrombocythemia. A wide range of marrow colony-forming capacity values was noted early in disease courses; however, in 26 of 33 patients decreased colony-forming capacity was associated with disease transformation into acute myeloid leukemia or other clinically aggressive stages. An increased proportion of abnormally light buoyant density (less than 1.062 g/cm3) colony-forming cells was present in the marrow and peripheral blood of 15 of 16 patients with chronic myeloid leukemia, subacute myeloid leukemia, preleukemia or essential thrombocythemia; in seven of eight patients with greater than 35 per cent abnormally light colony-forming cells their disease subsequently underwent transformation. Elevated levels of urinary colony-stimulating factor output were noted in 17 of 31 patients, and in 10 of 12 patients whose disease subsequently underwent acute transformation within 10 months of study. In six of seven patients who simultaneously had an increased urinary output of colony-stimulating factor and low colony-forming capacity in marrow, transformation occurred within 10 months. These findings indicate that progressive abnormalities of both marrow clonal growth patterns and levels of possible humoral regulatory substances develop during evolution of these diseases. In contrast, patients with idiopathic sideroblastic ineffective erythropoiesis had normal values for marrow colony-forming capacity, proportion of light density colony-forming cells and urinary colony-stimulating factor output, and in none has their disease transformed into acute myeloid leukemia. These in vitro studies appear useful for clinical staging, evaluating prognosis and categorizing patients with myeloproliferative disorders.
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PMID:The myeloproliferative disorders. Correlation between clinical evolution and alterations of granulopoiesis. 108 34

Diagnosing chronic myeloproliferative disorders (CMPD) can be difficult because of overlap and possible transitions between the different conditions and their similarity to reactive myeloproliferations. DNA analysis was applied to improve differentiation of CMPDs. All subtypes of CMPD analyzed, including chronic myeloid leukemia, agnogenic myeloid metaplasia, polycythemia vera, and essential thrombocythemia, had in common that granulocytes and bone marrow cells were clonal in origin, as shown by X chromosome-linked DNA polymorphism in conjunction with methylation patterns (n = 32). Reactive myeloproliferations, by contrast, showed polyclonal inactivation patterns. Clonality could not distinguish CMPD from cases of myelodysplastic syndrome because the latter (n = 7) also exhibited clonal hematopoiesis. Because of their clonal origin, peripheral granulocytes were used in all cases (n = 201) to detect bcr gene rearrangement. Despite possible morphologic overlap between different types of CMPD, bcr gene rearrangement was specific for chronic myeloid leukemia and could be applied to differentiate chronic myeloid leukemia from other CMPDs in cases of equivocal morphologic diagnosis. Chronic myeloproliferative disorders represent clonal hemopoietic diseases that probably have specific underlying genetic defects. Thus DNA analysis can aid substantially in the differential diagnosis of CMPD.
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PMID:DNA analysis to aid in the diagnosis of chronic myeloproliferative disorders. 161 25

A 51-year-old woman with no history of prior chemotherapy or radiation therapy was diagnosed with essential thrombocythemia (ET) according to the diagnostic criteria established by the Polycythemia Vera Study Group (PVSG). Cytogenetic analysis of bone marrow metaphases revealed both normal female karyotype and a single clonal abnormality, 46,XX,del(5)(q22q35). While chromosomal abnormalities have been reported in ET, their incidence is very low, and no specific abnormality has been found. Many of the reported cases of ET with chromosomal aberrations, including 5q-, do not meet the diagnostic criteria proposed by the PVSG, and may represent one of the other myeloproliferative disorders or a myelodysplastic syndrome. Furthermore, it is important to distinguish the 5q- syndrome, which may present with thrombocytosis and megakaryocytic hyperplasia, from ET. Our patient appears to be the first example of untreated ET clearly meeting the PVSG criteria in which 5q- was the only clonal abnormality seen at diagnosis.
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PMID:Deletion of the long arm of chromosome 5 in essential thrombocythemia. 833 Feb 75

Restriction fragment length polymorphisms (RFLP) of the X-chromosome genes phosphoglycerate kinase and hypoxanthine phosphoribosyl transferase were used in conjunction with cytogenetic analysis to study the clonality of hematopoiesis in four female patients with myelodysplastic syndromes, treated with either granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3), and in one patient with essential thrombocythemia (ET) treated with IL-3. Both conventional karyotyping and X-inactivation analysis demonstrated the persistence of a monoclonal pattern of hematopoiesis in the two patients with refractory anemia (RA) treated either with GM-CSF or with IL-3. The partial restoration of non-clonal hematopoiesis was observed in one patient with RA and an excess of blasts following treatment with a combination of GM-CSF and low dose cytosine arabinoside. In a fourth patient with RA and in the patient with ET, treatment with IL-3 resulted in the complete restoration of a non-clonal pattern of peripheral blood cells. In contrast, the bone marrow cells remained monoclonal by Southern blot analysis in the patient with RA in whom it could be tested. Non-clonal lymphocytes appear to have been released into the peripheral blood in the two latter cases and are responsible for the non-clonal RFLP pattern. These results suggest that cytokine therapy may have diverse effects on hematopoiesis, including the release of residual normal cells into the peripheral blood.
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PMID:In vivo effects of granulocyte-macrophage colony-stimulating factor and interleukin-3 on clonal and non-clonal cell populations in patients with clonal hematopoietic disorders. 167 79

A 57-year-old man was diagnosed to have essential thrombocythemia (ET) in July 1977. He was doing well with continual medication of carboquone but was hospitalized because of slight unconsciousness and gait disturbance in May, 1988. His laboratory data were as follows: WBC count 81,600/microliters with 55% of blasts with cytoplasmic blebs, Hb 10.2 g/dl, and platelet count 2.6 x 10(4)/microliters. Bone marrow aspiration revealed hypercellular marrow with 72.8% blasts. Chromosomal analysis showed tetraploidy with 7p+ and 19p+. Cytochemistry of blasts showed the positivity for platelet peroxidase and CDw 41. The diagnosis of acute megakaryoblastic leukemia was made. Meningeal leukemia was also suspected by the cerebrospinal fluid data, and cytarabine was intrathecally injected. Then the percent of blasts of peripheral blood gradually decreased and the data of cerebrospinal fluid improved. However, several days later the patient became comatose probably due to cerebral bleeding, and died. In this case, two possibilities were considered (1) that a blastic transformation to acute leukemia from ET, and (2) that a secondary leukemia developed as a result of the chemotherapy, independently of ET. Since there was no evidence of myelodysplastic syndrome, it was concluded that this case represented a blastic transformation of ET.
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PMID:[Acute megakaryoblastic leukemia developing 11 years after diagnosis of essential thrombocythemia]. 194 27

Sialyl Lewisx-i (SLX) was found in more than 40% of patients with acute leukemia or chronic myelogenous leukemia, and in about 20% of those with myelodysplastic syndrome or malignant lymphoma. This tumor marker was absent in all patients with polycythemia vera, essential thrombocythemia, primary myelofibrosis, chronic lymphatic leukemia, multiple myeloma, and those with acute leukemia or malignant lymphoma in remission. The marker was found in 8% and of the patients with idiopathic thrombocytopenic purpura and 33% of those with autoimmune hemolytic anemia but in no patient with aplastic anemia or megaloblastic anemia. Immunostaining with SLX antibody showed that tumor cells of the patients with high levels of serum SLX were producing the SLX antigen. The detection of this marker in the serum is thought to be useful not only in the diagnosis but also in the observation of the recurrence of the diseases.
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PMID:Evaluation of serum sialyl Lewisx-i in hematologic disorders. 207 71

Phase II study of YNK01 (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate), a derivative of cytosine arabinoside, on hematological malignancies was conducted by multi-institutional cooperative group. YNK01 was administered orally at dose of 100-300 mg/body/day for more than 2 weeks. The number of registered and evaluated patients were 211 and 156, respectively. Of 23 patients with acute myelogeneous leukemia (AML), 2 complete response (CR), one partial response (PR) were observed (CR + PR: 13.0%). Hypoplastic leukemia (1/4: 25%), acute unclassified leukemia (1/1: 100%). Of 45 patients with MDS, 2CRs, 6 good response (GR) and 5PRs were observed (CR + PR: 28.9%). AML developing after a prior history of MDS (5/17: 29.4%), CML-BC (2/9: 22.2%). Of 19 patients with CML, 9 achieved CR, 3 achieved PR (63.2%). Of 11 patients with polycythemia vera, 4 achieved CR, 5 achieved PR (81.8%). Of 6 patients with essential thrombocytosis, 2 achieved CR, one achieved PR (50%). The major adverse effects included gastrointestinal toxicities such as nausea, vomiting, anorexia, diarrhea, and elevation of GOT and GPT which were tolerable and reversible. This study indicates that YNK01 is a useful agent against acute leukemia and MDS, especially RAEB, RAEB in T, CMMoL.
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PMID:[Phase II study of YNK01 (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate) on hematological malignancies]. 226 Aug 76

Using the megakaryocytic leukemia cell lines, K-562 and CMK established from a Down's patient with acute megakaryoblastic leukemia, we studied the changes of antigen expression, cytosolic Ca2+ mobilization, thromboxane (TX) A2 formation and gene expression during megakaryocyte differentiation. We found that thrombospondin synthesis and platelet factor (PF)-4 gene expression were specific for mature megakaryoblasts, whereas collagen unresponsiveness and prostaglandin E1-induced Ca2+ mobilization were noted in immature megakaryoblasts alone. This experiment shows that functional and genetic analysis are useful for characterizing the leukemic megakaryoblastic cells. We analyzed the clinical, hematologic and genetic features of 4 patients with M7, and acute megakaryoblastic transformation of CML, MDS and essential thrombocythemia. In two patients, prednisolone and 6-MP were effective in cytoreduction. In 3 patients with increased platelet counts, normal CFU-Meg formation, the megakaryoblasts with platelet production, or the coexistence of immature megakaryoblasts with mature megakaryocytes were observed, thus indicating that some megakaryoblastic leukemia cells still have the capacity of differentiation. One patient had megakaryoblastic cells with PF-4 gene expression. These clinical findings suggest that the megakaryoblastic leukemia could not be characterized as usual leukemia and a more sensitive marker is required to differentiate leukemic megakaryoblasts from normal megakaryoblasts.
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PMID:[Megakaryocytic leukemia cell lines and megakaryocytic leukemia]. 238 Oct 77

Eighty-one consecutive hydroxyurea-treated patients with Philadelphia (Ph) chromosome negative chronic myeloproliferative disease were followed prospectively from 1981 to 1989; 35 of them had polycythemia vera, 32 had essential thrombocythemia, 12 had myelofibrosis, and 2 had myeloproliferative syndromes. The 81 patients were treated with hydroxyurea for a total of 3,804 months during the observation time. Only three patients had been treated with alkylating agents or 32P before start of hydroxyurea treatment. Four patients transformed into acute myeloid leukemia or myelodysplastic syndromes; three of these patients had essential thrombocythemia, and one had a myeloproliferative syndrome. Two patients died of solid cancers. Five out of 53 evaluable patients (9%) had pretreatment clonal cytogenetic abnormalities involving chromosomes 1, 9, 20, and 21. At follow-up, during or after hydroxyurea treatment, 15% had cytogenetic abnormalities, an unexpectedly low frequency compared to the previously reported frequency in patients with polycythemia vera treated with alkylating agents. None of our patients who developed cytogenetic clonal changes during hydroxyurea therapy had polycythemia vera. However, follow-up is too short to draw any conclusions about the mutagenic potential of hydroxyurea compared to alkylating agents.
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PMID:Cytogenetic abnormalities and leukemic transformation in hydroxyurea-treated patients with Philadelphia chromosome negative chronic myeloproliferative disease. 239 74


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