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

Several studies have demonstrated the prognostic value of cytogenetic analysis in MDS both for survival and progression to AML. However it is unknown which are the numerical or structural abnormalities required for leukemic transformation. In this report we studied clinically and cytogenetically 127 patients: 125 with primary MDS and two with AML with a previous history of MDS. Thirty-one patients (24%) showed evolution of the disease during the follow-up study. Chromosomal abnormalities found at diagnosis in patients that progressed toward AML included: del(5)(q15), +6, del(6)(q21), t(5;8)(q32;q22),-7, del(7)(q22), der(7)t(1;7)(q10;p10), t(7;11)(p15;p15), +8, del(11)(q23), del(12p), del(3)(q21), del(20)(q12) and complex karyotypes. Eight of these patients were studied cytogenetically during transformation and showed acquisition of chromosomal alterations involving dup(1q), +8, del(11)(q23), and translocations between chromosomes 1 and 8 or 7 and 17. In addition we also observed gain of ploidy and monosomy 21. These results suggest that chromosomal alterations during evolution of the disease include special chromosome gains or abnormalities of chromosomes 1, 7, 8, 11 and 17 with involvement of ETV-1, Hox-A9, Pax 4, MLL genes besides a putative gene mapped at 17q25. We also applied the International Prognostic Scoring System (IPSS) to 114 patients, excluding those submitted to allogeneic bone marrow transplant. Our patients were classified into four distinct risk groups. The analysis of risk groups presented by 27 patients who showed evolution of the disease revealed 18 at the high risk group and four at the intermediate-2 group. From the intermediate-1 risk group only five patients showed evolution of the disease. Three of these patients evolved from RA to RAEB with gain of a del(11)(q23) or an expansion of a del(12)(p12) clone. Our results suggest that some chromosomal alterations are responsible for each step in the evolution of the disease. As the pathway of evolution is not unique it has been very difficult to define what genetic alteration comes first. However from several results in the literature and our own, it seems that some chromosomal alterations may predict the evolution of the disease and are correlated with short survival, as for example the trisomy of chromosome 8, and might be incorporated in the high risk group in the IPSS. This score system has been proved to be useful for predicting survival and evolution from MDS to AML.
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PMID:Chromosomal alterations associated with evolution from myelodysplastic syndrome to acute myeloid leukemia. 1099 2

We report a case of de novo myelodysplastic syndrome with clonal eosinophilia (MDS-Eo) and eosinophilic pulmonary interstitial infiltration, confirmed by autopsy. Cytogenetic study using Giemsa banding identified 47,XY,+1,der(1;7)(q10;p10),+8 in the marrow cells. Simple Giemsa staining revealed the same chromosomal aberration in metaphase spreads with eosinophilic granules, indicating the clonal proliferation of eosinophils. To our knowledge, our case is the 6th reported case of MDS-Eo with cytogenetically confirmed clonal eosinophilia, and the first autopsy of MDS-Eo. A review of the literature combined with our findings suggests that this type of chromosomal aberration might be involved in the as yet unknown pathogenesis of MDS-Eo.
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PMID:Myelodysplastic syndrome with clonal eosinophilia accompanied by eosinophilic pulmonary interstitial infiltration. 1115 87

Conventional cytogenetic analysis is limited in the evaluation of plasma cell disorders because, relative to normal hematopoietic elements, plasma cells divide slowly. Moreover, it is difficult to know whether abnormal metaphases originate from malignant plasma cells or myeloid cells harboring other abnormalities. We studied a patient with primary systemic amyloidosis who had previously been treated with an alkylating agent. Bone marrow cells were analyzed by cytoplasmic-immunoglobulin fluorescent staining combined with fluorescent in situ hybridization (cIg-FISH). Both chromosome enumeration probes for chromosome 1 and 7 and loci-specific probes for the short and long arm of chromosome 7 were used. Cytogenetic analysis disclosed the following abnormality: +der(1;7)(q10;p10). On cIg-FISH, the myeloid cells had fusion signals between chromosome enumeration probes for chromosomes 1 and 7, whereas plasma cells had the normal appearance of two pairs of signals. There was a second clone of abnormal myeloid cells with monosomy of chromosome 7. The bone marrow did not show any evidence of myelodysplasia. Interphase cIg-FISH is a useful technique for assigning the lineage of chromosomal abnormalities in plasma cell disorders.
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PMID:Fish demonstrates treatment-related chromosome damage in myeloid but not plasma cells in primary systemic amyloidosis. 1134 20

In acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) there are frequently complex karyotypes with multiple structurally altered chromosomes, many of which are marker chromosomes of unknown origin. The aim of this study was to apply comparative genomic hybridization (CGH) to cases of AML or MDS in transformation submitted for routine cytogenetic analysis to investigate whether this approach would yield any further information and, if possible, to predict which cases would benefit from CGH analysis. Nineteen cases with AML or MDS in transformation were analyzed. CGH revealed nine cases with gains or losses of chromosomal material. In six of these cases the chromosomal location of this material was not apparent from cytogenetic analysis especially when multiple markers were present. By using fluorescence in situ hybridization (FISH) with specific libraries for the chromosome regions that showed discordance between CGH and conventional cytogenetics, we were able to identify the chromosome location of material within the karyotype. In this group of six patients, four cases of an unbalanced translocation involving regions of chromosomes 5 and 17 were characterized. Three of these cases had additional abnormalities, including two cases with regions of amplification in which oncogenes are located (MYC, MLL) and one case with a dic(7;21)(p10;p10). In all six cases it was possible to characterize complex chromosomal aberrations such as derivative chromosomes, marker chromosomes, and ring chromosomes. This study demonstrates that CGH can detect true gain and loss of critical chromosome regions more accurately than conventional karyotyping in cases with very complex karyotypes, and can thus prove useful in predicting prognosis and pinpointing areas of the genome that require further study. Also, CGH can be a useful technique to identify the origin of marker chromosomes, and it can assist in choice of probes for confirmatory FISH, when there is no clue provided from the analysis of G-banded chromosomes.
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PMID:The application of comparative genomic hybridization as an additional tool in the chromosome analysis of acute myeloid leukemia and myelodysplastic syndromes. 1134 75

Megaloblastic anemia (MA) due to vitamin B12 deficiency is a reversible form of ineffective hematopoiesis. Myelodysplastic syndrome (MDS) is an acquired, irreversible disorder of ineffective hematopoiesis, characterized by stem cell dysfunction as a consequence of DNA damage manifested in part by karyotype anomalies. Importantly, MA and MDS are generally considered mutually exclusive diagnoses. We report the case of a 73-year-old woman with a profound macrocytic anemia, monocytosis and neurologic symptoms. Low cobalamin levels and the presence of anti-intrinsic-factor antibodies definitively established a diagnosis of pernicious anemia. Replacement therapy resulted in resolution of neurologic findings and macrocytosis; however, the anemia and monocytosis persisted. Bone marrow biopsy revealed trilineage myelodysplasia, which together with the peripheral monocytosis suggested a diagnosis of chronic myelomonocytic leukemia. Karyotype analysis revealed a clone with 45, XX, +der(1;7)(q10;p10)-7 [20]. Eighteen months after documented vitamin B12 replenishment her MDS transformed to terminal acute myeloid leukemia with the same clonal abnormality. Reversible cytogenetic abnormalities have been observed with MA, occasionally including karyotypes typically associated with MDS or myeloid leukemias. These abnormalities, like the anemia, resolve with vitamin replacement. This case suggests that MA and MDS can occur simultaneously; clinicians should be aware that this phenomenon occurs. Whether acquired karyotype abnormalities from the MA were related to the MDS and subsequent myeloid leukemia in this woman is a speculative but intriguing consideration that is discussed.
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PMID:Concurrent pernicious anemia and myelodysplastic syndrome. 1140 Oct 93

Clonal cytogenetic abnormalities are found in about 50% of all patients with myelodysplastic syndrome (MDS) and the clinical implication of these abnormalities is now well documented. However, the de novo appearance of balanced translocations in MDS patients during the progression of the disease is rarely reported and the significance of the balanced translocation remain to be elucidated. We report here the first case of refractory anemia with excess blasts in transformation (RAEBt), in which a new chromosomal translocation, t(7;13)(q10;q33) appeared de novo in the AML phase. It has been revealed that rearrangements and deletions of chromosome 7, i.e. der(1;7)(q10;p10), are very complex and that multiple regions may contribute to the disease phenotype and progression. Our case suggests that the chromosomal region at 7q10, rather than 1p10, might be one of the hot spots for myeloid proliferative disorders, including MDS.
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PMID:De novo appearance of t(7;13)(q10;q33) in the leukemic phase of myelodysplastic syndrome: a case report. 1193 62

The existence of isolated cytopenia in myelodysplastic syndrome (MDS) has been described, however, the exact clinico-hematologic features of such MDS patients are still obscure. The aim of this study was to provide additive clinico-hematologic information on MDS patients with isolated thrombocytopenia in comparison with idiopathic thrombocytopenic purpura (ITP). We searched for MDS with isolated thrombocytopenia in 146 sequential patients with MDS and evaluated their clinical features at the time of MDS diagnosis. We found 13/146 (8.9%) patients with MDS showing isolated thrombocytopenia. These patients were male predominant (10:3) and were all diagnosed as refractory anemia after reassessment of marrow findings, however, two of them had an initial diagnosis of ITP. Leukemic transformation was rarely noted (1/13 patients), but 1 patient developed myelofibrosis. Cytogenetic study demonstrated that 3 patients had del(20q), 2 had t(1;7)(q10;p10), and 5 showed normal karyotypes. The most prominent morphologic feature in the megakaryocytes was the presence of micromegakaryocytes (5/13) and 8/13 had hypogranulated neutrophils, whereas pseudo-Pelger nuclear anomaly was rarely detectable. Of note is that 7/13 patients had an increased number of megakaryocytes in the marrow. Most patients survived for more than 2 years. Approximately 9% of MDS patients showed isolated thrombocytopenia and most of them had a favorable prognosis. Some MDS patients with isolated thrombocytopenia have been mistakenly diagnosed as having ITP, since approximately 50% of our MDS patients with isolated thrombocytopenia had an increased number of megakaryocytes with low grade dysplasia. Therefore, careful attention to differential diagnosis is recommended for these patients.
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PMID:Clinico-hematologic features of myelodysplastic syndrome presenting as isolated thrombocytopenia: an entity with a relatively favorable prognosis. 1276 43

An unbalanced translocation der(1;7)(q10; p10) is a nonrandom chromosomal aberration commonly observed in myelodysplastic syndrome and acute myeloid leukemia. We molecularly analyzed the breakpoints of der(1;7)(q10;p10) by quantitative fluorescent in situ hybridization (FISH) analyses using centromeric satellite DNAs mapped to chromosomes 1 and 7 as probes. We found that the signal intensities of 2 centromere alphoid probes, D1Z7 on chromosome 1 and D7Z1 on chromosome 7, were almost invariably reduced on the derivative chromosome compared with those on their normal counterparts. These results suggest that this translocation results from the recombination between the 2 alphoids, which was further confirmed by fiber FISH experiments. Because the relative reduction in the intensities of D1Z7 and D7Z1 signals on the derivative chromosomes was highly variable among patients, it was estimated that the breakpoints in these patients were randomly distributed over several megabase pairs within each alphoid cluster except for its extreme end to the short arm. Our results provide a novel insight into the structural basis for generation of this translocation as well as its leukemogenic roles.
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PMID:Molecular characterization of the recurrent unbalanced translocation der(1;7)(q10;p10). 1281 70

A recurring translocation (X;20)(q13;q13) was found in four women ranging in age from 57 to 77 years. They had myelodysplasia, myelodysplasia with thrombocytopenia and pancytopenia, transforming to myelofibrosis, and myelodysplasia with sideroblastic anemia, respectively. The t(X;20) was the sole abnormality in three cases; one case also had a der(1;7)(q10;p10). Added to three previously reported cases, our four cases bring the total to seven; thus, t(X;20)(q13;q13) is a nonrandom translocation associated with myeloid disorders. Previous FISH studies showed that the breakpoint on the X is proximal to XIST. In one of our cases, the breakpoint on the X was shown to be proximal to Xq12, by FISH using a probe for the androgen receptor gene locus.
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PMID:Translocation (X;20)(q13;q13.3): a nonrandom abnormality in four patients with myeloid disorders. 1567 51

A 70-year-old man with B-cell chronic lymphocytic leukemia (CLL) received single-agent treatment with the purine analogue fludarabine, which led to complete remission. After 8 years, he presented with pancytopenia. Marrow examination showed acute myeloid leukemia (AML) with trilineage myelodysplasia (MDS). Cytogenetic analysis showed an unbalanced der(1;7)(p10;q10) that resulted effectively in deletion 7q; confirming the diagnosis of therapy-related AML (t-AML). No residual CLL was present. Together with previous reports of secondary cancers after fludarabine treatment and the association of monosomy 7/7q- with another purine analogue azathioprine, results suggest that t-AML might develop after fludarabine therapy.
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PMID:Therapy-related acute myeloid leukemia after single-agent treatment with fludarabine for chronic lymphocytic leukemia. 1668 Jul 54


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