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)

Multicolor fluorescence in situ hybridization (M-FISH) was performed on bone marrow cells of 116 unselected cases of therapy-related myelodysplasia (t-MDS) or acute myeloid leukemia (t-AML), and the results were compared with those of previously performed with G-banding. Among 18 patients with a normal karyotype, no cryptic chromosome aberrations were observed with M-FISH. In 56 patients with a previously solved abnormal karyotype, only 17 new aberrations were identified, whereas 153 new aberrations were detected by M-FISH in 42 patients with a previously unsolved karyotype. In total, 112 of the new aberrations were unbalanced translocations, and only nine were balanced translocations. A clustering of breakpoints was observed in the centromeric or pericentromeric region of chromosomes 1, 5, 7, 13, 17, 21, and 22 in 48 of 98 patients with t-MDS and t-AML and an abnormal karyotype, and was related to previous therapy with alkylating agents. In seven of eight patients with chromosome derivatives containing material from three or more chromosomes or having sandwichlike chromosomes, those made up of several small interchanging layers of material from two chromosomes showed mutations of TP53. M-FISH had little impact on the prognostic classification of t-MDS and t-AML, as only three patients changed prognostic groups as a result of M-FISH.
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PMID:Centromeric breakage and highly rearranged chromosome derivatives associated with mutations of TP53 are common in therapy-related MDS and AML after therapy with alkylating agents: an M-FISH study. 1564 89

Myelodysplastic syndromes are clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis and peripheral cytopenias. Telomeres are thought to be critical in maintaining normal hematopoiesis. In this study, we assessed telomere dynamics in order to obtain further insight into the pathogenesis of MDS. We studied telomerase activity (TA) in mononuclear cells from peripheral blood (PB) and bone marrow (BM) from patients with myelodysplastic syndrome (MDS; n=24), acute myeloid leukemia (AML; n=14), chronic myeloid leukemia (CML; n=12) and 11 normal controls using a polymerase chain reaction-based telomeric repeat amplification assay. Telomerase activities (mean+/-S.D.) were found as 0.199+/-0.09, 0.414+/-0.55, 0.253+/-0.26 and 0.181+/-0.05 pg/ml in PB mononuclear cells, respectively (P>0.05). Comparison of TA of BM mononuclear cells from 19 MDS patients versus 10 BM samples from normal controls revealed no significant difference (P=0.3). There was no correlation between the levels of TA and clinical and prognostic parameters of the patients with MDS, such as degree of anemia, platelet counts on presentation, gender, presence of organomegaly, bone marrow fibrosis and BM blast percentages. Patients who had higher TA had significantly inferior survival compared with patients who had lower TA (P=0.005). Consistent with previous data, our results suggest that in patients with MDS, telomerase activity might be insufficient to compensate for the telomere shortening. Furthermore, TA might be prognostically important in patients with MDS. Measurements of enzymatic activity in association with telomere length studies may help to understand the prognostic role of telomere dynamics in patients with myelodysplastic syndromes more reliably.
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PMID:Telomerase activity in myelodysplastic syndromes. 1611 31

Deletions or translocations of chromosome band 13q14, the locus of the retinoblastoma gene (RB1), have been observed in a variety of hematological malignancies including myelodysplastic syndrome (MDS). We describe here a novel unbalanced translocation der(13)t(7;13)(p13;q14) involving 13q14 in a patient with MDS. A 66-year-old woman was diagnosed as having MDS, refractory anemia with excess of blasts (RAEB-1) because of 7.4% blasts and trilineage dysplasia in the bone marrow cells. G-banding and spectral karyotyping analyses showed complex karyotypes as follows: 46,XX,der(6)t(6;7)(q11;?),der(7)del(7)(?p13)t(6;7)(q?;q11)t(6;13)(q?;q?),der(13)t(7;13)(p13;q14). Fluorescence in situ hybridization (FISH) analyses demonstrated that one allele of the RB1 gene and the microsatellite locus D13S319, located at 13q14 and telomeric to the RB1 gene, was deleted. Considering other reported cases, our results indicate that submicroscopic deletions accompanying 13q14 translocations are recurrent cytogenetic aberrations in MDS. The RB1 gene or another tumor suppressor gene in the vicinity of D13S319, or both, may be involved in the pathogenesis of MDS with 13q14 translocations by monoallelic deletion.
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PMID:A der(13)t(7;13)(p13;q14) with monoallelic loss of RB1 and D13S319 in myelodysplastic syndrome. 1621 65

Chromosome rearrangements are found in many acute leukemias. As a result, genes at the breakpoints can be disrupted, forming fusion genes. One of the genes involved in several chromosome aberrations in hematological malignancies is NUP98 (11p15). As NUP98 is close to the 11p telomere, small translocations might easily be missed. Using a NUP98-specific split-signal fluorescence in situ hybridization (FISH) probe combination, we analyzed 84 patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia, or myelodysplastic syndrome with either normal karyotypes or 11p abnormalities to investigate whether there are unidentified 11p15 rearrangements. Neither NUP98 translocations nor deletions were identified in cases with normal karyotypes, indicating these aberrations may be very rare in this group. However, NUP98 deletions were observed in four cases with unbalanced 11p aberrations, indicating that the breakpoint is centromeric of NUP98. Rearrangements of NUP98 were identified in two patients, both showing 11p abnormalities in the diagnostic karyotype: a t(4;11)(q1?3;p15) with expression of the NUP98-RAP1GDS1 fusion product detected in a 60-year-old woman with AML-M0, and an add(11)(p15) with a der(21)t(11;21)(p15;p13) observed cytogenetically in a 1-year-old boy with AML-M7. JARID1A was identified as the fusion partner of NUP98 using 3' RACE, RT-PCR, and FISH. JARID1A, at 12p13, codes for retinoblastoma binding protein 2, a protein implicated in transcriptional regulation. This is the first report of JARID1A as a partner gene in leukemia.
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PMID:Identification of NUP98 abnormalities in acute leukemia: JARID1A (12p13) as a new partner gene. 1641 55

We present a 30-year-old male patient diagnosed with myelodysplastic syndrome (MDS). Chromosome analysis of the bone marrow aspirate revealed a derivative chromosome resulting from an unbalanced 1;16 translocation causing the gain of 1q and loss of 16q. Dual color fluorescence in situ hybridization demonstrated that the 1q;16p derivative chromosome contained centromeric material derived from chromosome 1, and accordingly the translocation was designated as a der (1)t(1;16)(p11;p11.1). Review of literature revealed that 1;16 translocation in MDS is nonrandom and is always described as unbalanced, resulting in trisomy 1q and monosomy 16q.
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PMID:Myelodysplastic syndrome with an unbalanced 1;16 translocation in a case of early age of onset. 1709 74

We report a patient with myelodysplastic syndrome (refractory anemia) showing the karyotype 46,XY,+1,der(1;10)(q10;p10), resulting in trisomy 1q and monosomy 10q abnormality. This finding suggests that either trisomy of 1q or centromeric connection between chromosomes 1 and 10, rather than the absence of 10q, might be essential toward neoplastic transformation.
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PMID:Recurrent unbalanced whole-arm t(1;10)(q10;p10) in myelodysplastic syndrome: a case report and literature review. 1721 27

Chromosome rearrangements involving band 3q26.2 are associated with myeloid malignancies, aberrant expression of the human ecotropic virus integration site-1 (EVI1) gene, an unfavourable prognosis and an aggressive clinical course. The 3q26.2 rearrangements are characteristically heterogeneous and typically difficult to detect in poor quality metaphases. To develop a dual-colour fluorescence in situ hybridisation (FISH) assay for the detection of 3q26.2/EVI1 aberrations, a series of 10 BAC clones corresponding to the EVI1 gene region were systematically evaluated and narrowed down to two probe sets; one probe set encompassed the EVI1 gene extending centromeric, while the second probe set covered the EVI1 gene and extends telomeric. Both probe sets were evaluated on 35 patient samples with cytogenetically defined 3q26.2 rearrangements collected at various treatment time points, the inv(3)(q21q26.2) Kasumi-4 cell line, and 10 known negative samples. The two-probe set strategy identified all samples, despite the vast breakpoint heterogeneity observed. In samples from acute myeloid leukaemia and myelodysplastic syndrome cases, the majority of inversion breakpoints were 3' to EVI1 whereas 3q26.2 translocation breakpoints frequently mapped 5' to EVI1. However, two 3q26.2 translocation samples had breakpoints 3' to EVI1. Most inv(3q) chronic myeloid leukaemia samples showed breakpoints within the EVI1 gene. This study demonstrated that, despite the extensive breakpoint heterogeneity observed with 3q26.2 aberrations, this FISH strategy is effective for the detection of 3q26.2 abnormalities in myeloid malignancies.
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PMID:An interphase fluorescence in situ hybridisation assay for the detection of 3q26.2/EVI1 rearrangements in myeloid malignancies. 1734 Dec 66

Though X chromosome anomalies are uncommon in hematologic malignancies, isodicentric X chromosomes, idic(X)(q13), with break and fusion points at Xq13 are well known among older females with de novo myelodysplasia. In contrast, only 17 patients with X isochromosomes involving break and fusion points at the centromere i(X)(p10) have been published, to our knowledge. We present 14 new patients with i(X)(p10) identified by G-banding and further characterized by fluorescence in situ hybridization (FISH) using probes for the X p-arm, X alpha-satellite DNA (DXZ1), and the XIST gene (Xq13). These anomalies each had an X p-arm probe signal on either side of a single centromeric FISH signal, thus they are monocentric isochromosomes. On the basis of FISH, the following three centromeric patterns were identified: (1) centromere signal same size as normal X, (2) centromere signal larger than normal X, and (3) centromere signal smaller than normal X. These centromere patterns may be related to the mechanism of i(X)(p10) formation. In 9 (64%) of 14 patients, the i(X)(p10) was the sole anomaly, attesting to its pathogenic potential. Our series, when collated with information on previously reported cases of i(X)(p10), show that this anomaly is associated with females with a median age 74 years, though patients from 3.75 to 49 years, including a 17-year-old in the present cohort, have been described. i(X)(p10) is observed in a wide range of hematologic malignancies, including myeloid and lymphoid disorders, as well as a patient with therapy-related AML in the present series. i(X)(p10) has been reported in occasional males, indicating that this anomaly can arise from active X chromosomes. It is not known whether i(X)(p10) arises randomly from the active or inactive X chromosome in female patients.
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PMID:Isochromosome (X)(p10) in hematologic disorders: FISH study of 14 new cases show three types of centromere signal patterns. 1798 Dec 11

Dyskeratosis congenita (DC) is an inherited syndrome exhibiting marked clinical and genetic heterogeneity. It is characterized by multiple features including mucocutaneous abnormalities, bone marrow failure and an increased predisposition to cancer. Three genetic subtypes are recognized: X-linked recessive DC bears mutations in DKC1, the gene encoding dyskerin, a component of H/ACA small nucleolar ribonucleoprotein particles; autosomal dominant (AD) DC has heterozygous mutations in either TERC or TERT, the RNA and enzymatic components of telomerase, respectively, and autosomal recessive DC in which the genes involved remain largely elusive. Disease pathology is believed to be a consequence of chromosome instability because of telomerase deficiency due to mutations in DKC1, TERC and TERT; in patients with DKC1 mutations, defects in ribosomal RNA modification, ribosome biogenesis, translation control or mRNA splicing may also contribute to disease pathogenesis. The involvement of telomerase complex components in X-linked and AD forms and the presence of short telomeres in DC patients suggest that DC is primarily a disease of defective telomere maintenance. Treatment is variable and complicated by the development of secondary cancers but, being a monogenic disorder, it could potentially be treated by gene therapy. DC overlaps both clinically and genetically with several other diseases including Hoyeraal-Hreidarsson syndrome, aplastic anaemia and myelodysplasia, among others and its underlying telomeric defect has implications for a broader range of biological processes including ageing and many forms of cancer.
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PMID:Dyskeratosis congenita: a genetic disorder of many faces. 1800 59

Deletion of the long arm of chromosome 20 is a recurrent abnormality observed in myelodysplastic syndromes (MDS) and in Philadelphia-chromosome-negative myeloproliferative disorders (MPD). Our objective was to characterize the deletion size among 38 MDS and MPD patients using fluorescence in situ hybridization (FISH) with bacterial artificial chromosome (BAC) probes and to define commonly deleted and retained regions on chromosome 20. Patients were distributed in three groups according to the World Health Organization classification: MDS (22 patients), MPD (12 patients) and myelodysplastic/myeloproliferative diseases (four patients). FISH with centromeric, subtelomeric, and unique sequence probes was performed to characterize the deletion whereas its size was delineated using BAC clones. All 38 deletions were found to be interstitial. A commonly deleted region was identified for each of the three groups; it varied from 6.62 to 10.4 Mb and showed considerable overlapping. Two commonly retained regions (CRR), also showing overlapping, were identified in all three groups, one in the centromeric region, the other in the telomeric region. The deletion size is highly variable, with no apparent recurrent breakpoint. The deletion may result in the loss of one or several tumor suppressor genes but the target genes remain unknown. Loss of genes plays an important part in the myeloid leukemic process associated with del(20q). However, genes located in the retained chromosomal regions may also play a role in the oncogenetic mechanisms.
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PMID:Chromosome 20 deletions in myelodysplastic syndromes and Philadelphia-chromosome-negative myeloproliferative disorders: characterization by molecular cytogenetics of commonly deleted and retained regions. 1835 Feb 94


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