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)

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

To evaluate the incidence and the predictive signs of therapy-related myelodysplasia and/or acute myeloid leukaemia (tMDS/tAML), we undertook a prospective study over a 4-year period of 221 patients who underwent autologous haematopoietic progenitor cell transplantation. Only seven patients (3.1%) were identified to have tMDS/tAML. Peripheral cytopenia was the first sign; diagnosis could be achieved by cytological analysis of bone marrow smears using World Health Organization criteria. All patients presented with bi- or trilineage dysplasia. Haematopoietic reconstitution was significantly delayed in patients progressing to tMDS/tAML compared with the control group. Typical cytogenetic abnormalities were observed in five of seven patients. The mean time interval between transplantation and cytological diagnosis, or detection of cytogenetic abnormalities, was 20.0 months and 31.2 months respectively. Pantelomeric fluorescence analysis using quantitative fluorescence in situ hybridization enabled us to make two major observations: (i) the fluorescence intensity in metaphases of all autografted patients was weak, and highly variable between tMDS patients; (ii) a drastic reduction of the telomere fluorescence intensity was observed in two patients who rapidly evolved to acute leukaemia. In conclusion, early detection of tMDS/tAML could be achieved by close follow-up of the bone marrow repopulation, and confirmed by cytological bone marrow examination and cytogenetic study. Our results address the implication of several factors, such as the initial telomeric status, and the effect of cytogenetic abnormalities and clonal expansion on bone marrow repopulation.
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PMID:Therapy-related myelodysplasia and/or acute myeloid leukaemia after autologous haematopoietic progenitor cell transplantation in a prospective single centre cohort of 221 patients. 1282 52

The myelodysplastic syndromes (MDS) are a group of disorders characterized by peripheral pancytopenia despite normo- or hyper-cellular bone marrow. This is thought to be due to apoptosis of hematopoietic bone marrow cells, resulting in ineffective hematopoiesis. The heterogeneous nuclear ribonucleoprotein (hnRNP) B1 is involved in pre-mRNA processing and binds to telomeric cDNA repeats. The hnRNP B1 is a marker for early cancer. The aim of our study was to clarify the relationships between prognosis and apoptosis, telomerase activity (TA) and hnRNP expression in the bone marrow. The subjects were 51 patients with MDS, including patients with refractory anemia (RA) (n = 32), refractory anemia with ringed sideroblasts (RARS) (n = 1), refractory anemia with excess blasts (RAEB) (n = 7), refractory anemia with excess blasts in transformation (RAEB-t) (n = 8) and chronic myelomonocytic leukemia (CMMoL) (n = 3). We also studied 6 cases with acute myelogenous leukemia (AML) arising from MDS (AML-MDS) and 10 control subjects. Bone marrow biopsies were stained immunohistochemically for caspase-3 (marker of apoptotic activity) and human telomerase reverse transcriptase (hTERT), and hnRNP B1. Fatal pancytopenia was the cause of death in 19 of the 51 patients. The caspase-3 positive cell rate was higher in MDS (16.3%) than in controls (4.4%) and AML-MDS (0.5%). The percentage of hnRNP B1-positive cells was higher in MDS (15.3%) and AML-MDS (56.3%) than in controls (5.6%). In MDS, hnRNP B1 levels were higher in RAEB and RAEB-t subtypes than in RA and RARS. The percentage of hTERT-positive cells was higher in AML-MDS (50.0%) than in controls (20.2%) and MDS (23.6%). Our findings suggest that activation of apoptosis occurs in MDS in the absence of hTERT expression, implicating high apoptosis in the absence of high TA with ineffective hematopoiesis. Poor prognosis correlated with higher caspase-3 and lower hTERT rates. In MDS, hnRNP B1 activity may be associated with leukemic transformation.
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PMID:Imbalance between apoptosis and telomerase activity in myelodysplastic syndromes: possible role in ineffective hemopoiesis. 1295 27

Rarely, myelodysplastic syndrome (MDS) is complicated by an acquired form of alpha-thalassemia (alpha-thalassemia in myelodysplastic syndrome [ATMDS]) characterized by hypochromic, microcytic, anisopoikilocytic red blood cells with hemoglobin H (HbH) inclusions. Acquired mutations in ATRX, a chromatin remodeling gene, have recently been found in 12 patients with typical features of ATMDS, though they have not been detected in MDS patients with similar red blood cell findings but little HbH. The alpha-globin genes themselves have appeared normal in all ATMDS patients studied to date. Here we characterize the molecular defect in a unique MDS patient with rare HbH inclusions in which an abnormal clone lost a greater than 1.9-Mb segment of the telomeric region of the short arm of one allele of chromosome 16, including both alpha-globin genes. Red blood cell changes associated with this acquired somatic genotype (--/alpha alpha) are surprisingly severe, demonstrating that a minor globin chain imbalance may be unexpectedly deleterious during the abnormal erythropoiesis that occurs in the context of MDS.
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PMID:Deletion of the alpha-globin gene cluster as a cause of acquired alpha-thalassemia in myelodysplastic syndrome. 1457 55

Telomeres represent the nucleoprotein tails of chromosomes that get shortened with each cell division. When the telomere length reaches a critical point, cell senescence and death occur. Telomerase is a reverse transcriptase that counteracts telomere loss by adding telomeric sequences. In patients with acquired aplastic anemia, the mean telomere length (TRF) of peripheral blood leukocytes is generally short when compared to normal controls, without it being clear whether a relationship between TRF and disease severity exists. Additionally, increased telomerase activity (TA) is found in the bone marrow mononuclear cell population (MNCs) of aplastic anemia patients, especially in the chronic form of the disease. Fanconi anemia (FA) patients generally demonstrate increased TA and short telomeres in peripheral blood MNCs, a fact attributed to the high turnover of hematopoietic progenitor cells in combination with direct breakages at telomeric sequences. Furthermore, a strong correlation has been shown between TRF and the severity of aplastic anemia, but not with FA evolution towards myelodysplastic syndrome or acute myeloblastic leukemia. In respect of dyskeratosis congenita (DC), a disease of either X-linked or autosomal dominant/recessive inheritance which is characterized by premature ageing of highly regenerative tissues, studies have been carried out in order to elucidate whether the X-linked DC is caused by a defect in ribosomal RNA processing and/or telomere maintenance. Finally, the direct genetic link established between DC pathogenesis and short telomeres may lead to the development of new therapeutic protocols for diseases characterized by short telomere length and subsequent genomic instability.
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PMID:Telomere length variation and telomerase activity expression in patients with congenital and acquired aplastic anemia. 1503 32

Robertsonian translocations are the most common constitutional structural abnormalities but are rarely reported as acquired aberrations in hematologic malignancies. The nonhomologous acrocentric rearrangements are designated as Robertsonian translocations, whereas the homologous acrocentric rearrangements are referred to as isochromosomes. Robertsonian rearrangements have the highest mutation rates of structural chromosome rearrangements based on surveys of newborns and spontaneous abortions. It would be expected that Robertsonian recombinations would be more common than suggested by the literature. A survey of the cytogenetics database from a single institution found 17 patients with acquired Robertsonian rearrangement and hematologic malignancies. This is combined with data from the literature for a total of 237 patients. All of the possible types of Robertsonian rearrangements have been reported in hematologic malignancies, with the i(13q), i(14q), and i(21q) accounting for nearly 60%. Complex karyotypic changes are seen in the majority of cases, corresponding with disease evolution. These karyotypes consistently show loss of chromosomes 5 and/or 7 in the myelocytic disorders, nonacrocentric isochromosomes, and centromeric breakage and reunion. However, nearly 25% of the acquired rearrangements were found as the sole abnormality or in addition to an established cytogenetic aberration. Most of these were the i(14q) with the myelodysplasia subtypes refractory anemia and chronic myelomonocytic leukemia.
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PMID:Acquired Robertsonian translocations are not rare events in acute leukemia and lymphoma. 1512 Sep 8

To assess the contribution of interphase fluorescence in situ hybridization (I-FISH) toward the detection of recurring unbalanced chromosomal anomalies at diagnosis, a systematic screening of -5/del(5)(q31), -7, and chromosome 8 aneuploidy was performed on 110 patients with acute myelocytic leukemia or high-risk myelodysplastic syndrome. We searched for monosomy 5/del(5q) by one-color I-FISH with a probe specific for the 5q31 region and for -7/8 by dual-color I-FISH with centromeric probes for chromosomes 7 and 8. Discrepancies between conventional cytogenetics (CC) and I-FISH were observed in 8 of the 110 patients (7.3%). For -5/del(5)(q31), a discordance was observed in two patients with complex abnormalities involving chromosome 5. Whereas no discordance was observed for -7, I-FISH detected a trisomy 7 unnoticed by CC in two cases. In six patients, I-FISH revealed a chromosome 8 aneuploidy not detected by CC. Our results illustrate that, when using this specific set of probes, I-FISH is of special interest for the detection of minor clones with chromosome 8 aneuploidy, breakpoint assessment, and sequence identification (markers). Also, to avoid misinterpretations, I-FISH should not be used alone at disease presentation, particularly in cases complex changes that have clearly established prognostic significance.
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PMID:Systematic screening at diagnosis of -5/del(5)(q31), -7, or chromosome 8 aneuploidy by interphase fluorescence in situ hybridization in 110 acute myelocytic leukemia and high-risk myelodysplastic syndrome patients: concordances and discrepancies with conventional cytogenetics. 1519 39

Translocations or deletions involving the 11q23 region have been observed in acute lymphoblastic leukemia (ALL), acute myelocytic leukemia (AML), myelodysplastic syndrome (MDS), and chronic lymphocytic leukemia (CLL). BAC probes encompassing the D11S29 and D11S924 markers and flanking the MLL gene were used in dual color fluorescence in situ hybridization. Fifteen patients with hematologic malignancies and cytogenetic abnormalities of 11q23 were analyzed. The BAC and MLL probes demonstrated split signals in five of 7 ALL or AML cases with translocations of 11q23. Of the remaining 2 cases, one had normal signals for both probe sets and the other had a submicroscopic deletion of the MLL 3' region. In one case of AML with del(11)(q23), deletion of the MLL 3' region and the region telomeric to the MLL gene was seen. Three CLL cases with deletion of part or the entire 11q23 region showed deletion of one copy of MLL, but retention of the region telomeric to MLL. However, in four MDS cases with deletions involving the 11q23 region, deletions of both the MLL gene and the flanking regions of the MLL gene were observed. Hence, the deletions on 11q23 are different but overlapping for CLL and MDS, implicating different genes involved for these diseases.
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PMID:Overlapping deletion regions at 11q23 in myelodysplastic syndrome and chronic lymphocytic leukemia, characterized by a novel BAC probe set. 1535 Mar 5

Cytogenetic abnormalities are observed in approximately one half of cases of myelodysplastic syndrome (MDS). Partial or complete chromosome losses and chromosome gains are frequently found, but there is a relatively high incidence of unbalanced translocations in MDS. We describe here two cases of MDS with an unbalanced translocation, der(11)t(11;12)(q23;q13). Both patients were 69 years of age and diagnosed with refractory anemia with excess of blasts in transformation (RAEB-t) according to the high percentage of blasts in the peripheral blood. Cytoplasmic hypogranulation of neutrophils was evident as a dysplastic change. The blasts were positive for CD4 and CD41a as well as CD13, CD33, CD34 and HLA-DR in both cases. Chromosome analysis showed complex karyotypes including a der(11)t(1;11)(q11;p15)t(11;12)(q23;q13) in case 1 and der(11)t(11;12)(q23;q13) in case 2 plus several marker chromosomes. Spectral karyotyping confirmed the der(11)t(11; 12)(q23;q13) and clarified the origin of marker chromosomes, resulting in del(5q) and del(7q). Fluorescence in situ hybridization (FISH) analyses with a probe for the MLL gene demonstrated that the breakpoints at 11q23 were telomeric to the MLL gene in both cases. FISH also showed that the breakpoint at 11p15 of the case 1 was telomeric to the NUP98 gene. Considering another reported case, our results indicate that the der(11)t(11;12)(q23;q13) is a recurrent cytogenetic abnormality and may be involved in the pathogenesis of advanced-stage MDS.
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PMID:Unbalanced translocation der(11)t(11;12)(q23;q13): a new recurrent cytogenetic aberration in myelodysplastic syndrome with a complex karyotype. 1552 5

In many patients with myelodysplastic syndromes or acute myeloid leukemia, complex chromosome aberrations can be seen, among which aberrations of chromosome 5 constitute a substantial part. With conventional cytogenetic technique, these aberrations are often identified as deletions or monosomy 5. We analyzed nine patients who, under conventional cytogenetic analysis, showed deletion or monosomy 5. We used fluorescence in situ hybridization with whole-chromosome painting probes to identify the counterpart chromosome and locus-specific identifiers for 5q31 and 5q33 approximately q34. A deletion of 5q was found concomitant with unbalanced translocations. Our results and cases from the literature showed that material from chromosome 5 could be translocated to almost all chromosomes. All patients but one had short survival; this one patient had a preserved 5q31 and 5q33 approximately q34 but a deletion of the q-arm more centromeric than these bands. In eight of the nine patients, further 14 translocations were revealed, not involving chromosome 5.
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PMID:Several chromosomes involved in translocations with chromosome 5 shown with fluorescence in situ hybridization in patients with malignant myeloid disorders. 1552 6


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