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

Trisomy 8 is the most common hyperdiploid numerical chromosomal abnormality that is found in myelodysplastic syndromes (MDSs). We explored the utility of combining fluorescence in situ hybridization interphase cytogenetics with routine morphologic analysis to characterize cases for which signs and symptoms were suggestive of MDS in which dysplastic changes were insufficient for a definitive diagnosis. Hybridization with a chromosome 8-specific centromeric probe was performed on bone marrow smears that were obtained from four patients with cytogenetically documented trisomy 8 and hematopoietic cell atypia that was suggestive but not diagnostic of MDS. Signals that corresponded to trisomy 8 were detected in 14.6% to 32.2% of the cells (detection threshold of trisomic clone, 5.0%). The conditions of two patients have remained hematologically stable with no disease progression, and these two patients are now considered to have refractory anemia. The conditions of the other two patients rapidly progressed to morphologically recognizable MDSs. This study demonstrates that the detection of trisomy 8 by fluorescence in situ hybridization can provide useful supplemental information in bone marrow specimens with morphologic changes that are suggestive of but not sufficient for a diagnosis of MDS. It should prove to be useful when standard cytogenetic analysis has not been performed or when it is not readily available.
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PMID:Detection of trisomy 8 by fluorescence in situ hybridization on bone marrow smears from patients with subtle myelodysplastic changes. 797 13

The molecular determination of the monoclonal or non-clonal nature of polycythemia cases is now possible in all or almost all females by study of the methylation pattern of several polymorphic X-linked loci. However, the techniques used are sophisticated and costly and the results do not clarify all cases. Karyotypic studies of PV, despite the number of cases reported thus far, remain insufficient. The natural history of cytogenetic events and their mechanisms of occurrence are still poorly known. Unsuccessful examinations are around 10-15%. The proportion of patients with clonal anomalies, 10-15% at diagnosis, increases with time, myelo-ablative treatments and evolution to myelofibrosis/myeloid metaplasia, so as to be close to 100% in cases with myelodysplasia/acute transformation. A few of the most frequently found non-random anomalies among which in particular trisomy 8 and 9, double trisomy 8+9, 20q- and trisomy of part or totality of 1q have some degree of specificity. Other recurring aberrations, such as 13q- mainly occur in late stages of PV, in which complex, unstable karyotypes are found. Finally none of those anomalies can be considered as a primary lesion. The frequency of clonal evolution is a matter of discussion. Despite their theoretical interest, PV cytogenetic results are of little diagnostic value, and as regards prognosis, they are statistically significant, but are of poor value in most individual patients. In conclusion, it is felt that clonality and karyotype studies should be pursued in PV, completed by "interphase cytogenetics" and molecular biology investigations, with theoretical aims rather than for immediate practical reasons.
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PMID:Clonality and karyotype studies in polycythemia vera. 803 35

One hundred eighty-eight unselected consecutive patients with "de novo" myelodysplastic syndrome (MDS) were studied cytogenetically. They were subclassified as 4 refractory anemia with ringed sideroblasts (RARS), 67 refractory anemia (RA), 58 refractory anemia with excess of blasts (RAEB), 40 RAEB in transformation (RAEB-t), and 19 chronic myelomonocytic leukemia (CMML). The overall incidence of chromosome abnormalities was 69%. The RAEB and RAEB-t patients showed karyotypic changes, more often than RA and CMML (76% and 100% vs. 56% and 42%, respectively). The most frequent single anomaly was del(5)(q13-q22q33) (22 cases), followed by monosomy 7 or del 7q (11 cases), del(11) (q14q23) (8 cases), trisomy 8 (4 cases). Complex karyotypes (defined by the presence of three or more structural or numerical abnormalities) were detected in 33 patients. With regard to the FAB classification, del (5)(q13q33) was associated with RA, and complex rearrangements with RAEB and RAEB-t. Leukemic transformation occurred in 66 patients (46%), none with a normal karyotype or del(11)(q14q23) as single abnormality. In patients carrying 5q- alone, acute evolution correlated with proximal breakpoint localization, being found in no case with del(5)(q13q33) but in three out of four cases with del(5)(q22q33). Acute leukemia (AL) progression happened in all cases with complex rearrangements and monosomy 7 or del(7q). Two of the four trisomy eight patients evolved in AL. By using the Cox proportional hazard regression analysis it was demonstrated that the karyotype abnormality was a significant predictor of leukemic transformation (P < 0.001). Patients with abnormal karyotypes without complex abnormalities had a survival (median survival 12 months) shorter than that of cases with only normal metaphases (median 83 months) (P < 0.001); patients with a mixture of normal/abnormal metaphases had a median survival of 31 months. The median survival for complex karyotypes was 7 months. Among cases with single defects, del(5)(q13q33) showed the best survival (64 months), monosomy 7 and del(7q) the worst (7 months) (P < 0.001).
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PMID:Karyotype in myelodysplastic syndromes: relations to morphology, clinical evolution, and survival. 803 76

In this report we describe the clinical and hematologic features of 23 cases of myelodysplasia (MDS) or acute megakaryoblastic leukemia (AMKL) occurring in Down's syndrome. MDS was characterized by thrombocytopenia, abnormal megakaryocytopoiesis, megakaryoblasts (< 30%) in the marrow and abnormal karyotype, the most common of which was trisomy 8, found in 7/15 patients with MDS. Three of five patients achieved a complete remission with low dose cytosine arabinoside, vincristine and retinyl palmitate. The high cure rate and the distinctive features of the leukemic process in these cases suggest that this type of MDS and AMKL are unique to patients with Down's syndrome.
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PMID:Myelodysplasia and acute megakaryoblastic leukemia in Down's syndrome. 813 85

Tetrasomy of chromosome 8 as a sole anomaly is apparently extremely rare in acute non-lymphocytic leukemia (ANLL): Only two cases have been reported, one of ANLL (M5b) with this karyotype. Very recently, another case was reported of a myelodysplastic syndrome (MDS) with isolated tetrasomy 8. We report tetrasomy 8 in four cases of ANLL, two of them with M5 and one with M1 subtype. Although in the latter case, tetrasomy 8 was evident in all karyotypes analyzed, in all other cases it constituted a subpopulation of cells other than those with trisomy 8 and those with a normal karyotype (in only one case another change was evident in the karyotype). Using fluorescence in situ hybridization (FISH), the proportion of tetrasomic cells was determined in interphase nuclei. By this technique, small cell populations (3-9%) were detected in three additional trisomy cases. An additional "control" group of five trisomy cases did not show a significant population of tetrasomic interphase nuclei. The data show that tetrasomy 8, if present as a sole anomaly in ANLL, may play a rather specific role for the subtype, and probably for the progression of myeloid neoplasia as well.
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PMID:Tetrasomy 8 as a clonal anomaly in myeloid neoplasias. 814 66

A 31-year-old woman presented with fever and arthralgia. Despite treatment with antimicrobials and corticosteroids, her symptoms persisted. A diagnosis of myelodysplastic syndrome (MDS)-refractory anemia (RA) was made by pancytopenia, dysplasia, and trisomy 8. Cultures of bone marrow, blood, and gastric juice showed Mycobacterium avium-intracellulare (MAI). She was treated with antimycobacterial drugs and recombinant human G-CSF/M-CSF and showed an initial response, but spike fever recurred and pancytopenia progressed. Hepatosplenomegaly and marked retroperitoneal lymphadenopathy were revealed, indicating further dissemination of MAI. Treatment with recombinant human GM-CSF and very-low-dose cytosine arabinoside, was started but was not effective. This case showed significant reduction in peripheral blood T-lymphocytes, especially the CD4+ population, and low immunoglobulin levels. Immunodeficiency state associated with long-term steroid therapy and MDS seemed to contribute to the development of the disseminated infection with MAI.
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PMID:Disseminated Mycobacterium avium-intracellulare infection in a patient with myelodysplastic syndrome (refractory anemia). 817 3

We report a female patient with Seckel syndrome who developed acute myeloid leukaemia at the age of 26 years. Analysis of bone marrow chromosomes showed an abnormal clone with abnormalities involving multiple chromosomes, including monosomy 7, trisomy 8, trisomy 11, and loss of the long arm of chromosome 5. After treatment with chemotherapy, the patient experienced severe toxicity with profound bone marrow aplasia and died of pneumonia two months later. We suggest that patients with Seckel syndrome may be at risk of developing myelodysplasia and acute myeloid leukaemia. They may also have poor tolerance to cytotoxic therapy.
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PMID:Acute myeloid leukaemia in a patient with Seckel syndrome. 818 23

As typical disorders of the elderly, myelodysplastic syndromes (MDSs) are relatively unusual in childhood. Nevertheless, up to 17% of cases of pediatric acute myeloid leukemia may have a preleukemic phase. In young patients, the goal of treatment is eradication of the preleukemic malignant clone and reconstitution of normal hematopoiesis. Allogeneic bone marrow transplantation (BMT) has proved to be capable of this, but the optimal conditioning treatment to achieve eradication remains to be defined. Between May 1989 and June 1993, eight consecutive pediatric patients with MDS received a marrow transplant from an HLA-identical, mixed lymphocyte culture (MLC) non-reactive sibling. Diagnosis at time of presentation was refractory anemia with excess of blasts (RAEB) in two patients, RAEB in transformation (RAEB-t) in three, and juvenile chronic myelogenous leukemia (JCML, the pediatric counterpart of adult chronic myelomonocytic leukemia) in the remaining three children. Conditioning regimen consisted of busulfan, cyclophosphamide and melphalan, three alkylating agents potentially capable of killing also dormant preleukemic stem cells. The preparative regimen was very well tolerated, and all patients engrafted promptly. Six out of eight patients (75%) are alive and well with a median observation time of 20 months (range 8-34 months). Serial karyotype monitoring and molecular analyses have demonstrated a full chimerism of donor cells and the complete disappearance of trisomy 8 detected before transplant in three cases. All surviving patients have a Karnofsky score of 100%. One boy, affected by RAEB-t with monosomy 7 resistant to treatment with low-dose ara-C, relapsed 11 months after BMT, evolved in AML and died from progressive leukemia. Another patient with RAEB died on day +95 after BMT due to interstitial pneumonia of unclear etiology. This study confirms that allogeneic BMT is the treatment of choice in pediatric patients with MDS, and suggests that the employed conditioning regimen is a safe and effective means for eradicating the preleukemic malignant clone. Particularly noteworthy is that the three children with JCML obtained a complete remission and one of them is now a long-term survivor.
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PMID:Busulfan, cyclophosphamide and melphalan as conditioning regimen for bone marrow transplantation in children with myelodysplastic syndromes. 818 40

Four patients with myelodysplastic syndrome (MDS), one with t(1;7) and three with trisomy 8, were studied by immunophenotyping and fluorescence in situ hybridization (FISH) to assess cell lineage involvement. The t(1;7) was detected using a biotin-labeled chromosome 1 centromere-specific DNA probe. This aberration was present in CD34-positive stem cells, the erythroid cell lineage (GPA+), and the granulocytic/monocytic (CD13+ and CD64+) cell lineages. We were not able to demonstrate the abnormality in the lymphoid cell lineages. In the patients with trisomy 8, the aberration was detected with chromosome 8 centromere-specific DNA probe or by chromosome in situ suppression hybridization (CISS) with a chromosome 8-specific library probe. The trisomy was detected in stem cells, erythroid precursor cells, megakaryocytes, and granulocytes/monocytes. In these MDS patients, the chromosome aberrations appear to occur only in cells of myeloid lineage.
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PMID:Cell lineage involvement in four patients with myelodysplastic syndrome and t(1;7) or trisomy 8 studied by simultaneous immunophenotyping and fluorescence in situ hybridization. 824 91

A simplified technique for fluorescent in situ hybridization (FISH) was used to investigate the prevalence of chromosomally abnormal clones in 13 cases of myelodysplastic syndrome (MDS). Biotinylated centromeric probes for chromosomes 7, 8, 12 and X, as well as painting probes for chromosomes 7 and 11, were applied to air-dried bone marrow smears stored from 6 to 23 months. Nine of the cases had been previously karyotyped, and five of these demonstrated normal karyotypes which were confirmed by FISH. The remaining four cases showed different chromosome changes. One case of sideroblastic anemia with chronic lymphocytic leukemia showed minor clones with either monosomy 12 (12% of cells) or tetraploidy (15% of cells) by FISH, whereas metaphase cytogenetics had demonstrated trisomy 12 in 20% of cells, with no evidence of tetraploidy. Another case which had been previously karyotyped was found to have a t(7;11) in 90% of cells while only 10% of cells were shown by FISH to contain this translocation. Monosomy 7 was demonstrated by FISH in a case of refractory anemia (RA), while trisomy 8 was found in a case of RA with excess blasts in transformation (RAEB-T), and in both of these cases the aneuploid clone was present in eosinophils as well as in erythroid and granulocytic precursors but not in lymphocytes or histiocytes, thereby demonstrating the value of FISH for identifying the affected cell lineage.
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PMID:Quantifying chromosome changes and lineage involvement in myelodysplastic syndrome (MDS) using fluorescent in situ hybridization (FISH). 828 3


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