UMLS:C0026986 - FACTA Search

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

Stored, fixed cell suspensions of bone marrows from 70 patients karyotyped over a three-year period for myelodysplastic syndrome (MDS) or related hematologic conditions were retrospectively studied in two series using centromeric probes for chromosomes 7 and 8. Series I consisted of patient samples with numerical and/or structural abnormalities of chromosomes 7 or 8, matched with chromosomally normal samples from about the same time period. Series II consisted of consecutive MDS patient samples as well as patient samples in which one or more cells had numerical or structural abnormalities of 7 and 8. In both series, probes for chromosomes 7 and 8 were applied in each case and at least 100 nuclei were scored for each probe for the distribution of one, two, or three signals. Twenty-seven cases had clonal abnormalities by routine cytogenetics (RC): 12 with monosomy 7; one with monosomy 8; five with trisomy 8; nine with clonal abnormalities other than 7 or 8 aneuploidy. Eleven cytogenetically normal cases gave abnormal interphase FISH (IF) results; one was subsequently confirmed by metaphase FISH analysis to have a clonal structural abnormality of chromosome 7; one case with a trisomy 8 clone, in remission by RC, showed 35% of cells by IF with three signals for chromosome 8; one case had heteromorphic chromosomes by FISH. Of eight remaining cases, five (four with -7 and one with +8 by IF) were among 22 cases of cytogenetically normal MDS. Three remaining cases (two with +8 and one with both +7 and +8 by IF) had AML or MPD. The high rate of possible undetected monosomy 7, among MDS cases in particular, suggests all MDS cases should be screened by IF.
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PMID:Fluorescence in situ hybridization to assess aneuploidy for chromosomes 7 and 8 in hematologic disorders. 1043 40

The ril gene encoding a LIM domain protein of an unknown function was previously identified by differential expression cloning as a candidate tumor suppressor gene in rat fibroblasts (Kiess, M., Scharm, B., Aguzzi, A., Hajnal, A., Klemenz, R., Schwarte-Waldhoff, I., Schafer, R., 1995. Expression of ril, a novel LIM domain gene, is down-regulated in HRAS-transformed cells and restored in phenotypic revertants. Oncogene 10, 61-68). Searching for novel genes on human chromosome 5q31.1 by the cDNA selection technique, we isolated a cDNA clone identical with the cDNA of the human RIL gene (GenBank Accession No. X93510). The human 5q31.1 region is of interest because it contains the cytokine gene cluster and is frequently deleted in the malignant cells of patients with myelodysplasia and myeloid leukemia. Using Southern blot analysis and restriction mapping of genomic YAC (yeast artificial chromosome) and cosmid clones, we located the human RIL gene 240-260 kb telomeric to the IRF1 gene and characterized its genomic structure. PCR analysis indicated the presence of two alternative RIL transcripts in human fetal brain mRNA. The major transcript is identical with the RIL cDNA previously deposited in GenBank and contains seven exons distributed over 14.5 kb of genomic DNA with the two last 3'-exons coding a LIM domain. The minor transcript lacks the sixth exon compared with the major transcript, which leads to the loss of the LIM domain. We also identified two putative transcription start points (tsp) and sequenced the 5'-flanking region of RIL to reveal potential binding sites for transcriptional factors.
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PMID:The human RIL gene: mapping to human chromosome 5q31.1, genomic organization and alternative transcripts. 957 74

The 5q- syndrome is a distinct type of myelodysplastic syndrome (MDS) characterised by refractory anaemia, morphological abnormalities of megakaryocytes, and del(5q) as the sole cytogenetic abnormality. In contrast to patients with therapy-related MDS with 5q deletions, 5q- syndrome patients have a favourable prognosis and a low rate of transformation to acute leukaemia. We have previously delineated a common deleted region of 5.6 Mb between the gene for fibroblast growth factor acidic (FGF1) and the subunit of interleukin 12 (IL12B) in two patients with 5q- syndrome and small deletions, del(5)(q31q33). The present study used fluorescence in situ hybridisation (FISH) analysis of these and a third 5q- syndrome patient with a small deletion, del(5)(q33q34), to refine further the critical deleted region. This resulted in the narrowing of the common deleted region within 5q31.3-5q33 to approximately 3 Mb, flanked by the adrenergic receptor beta 2 (ADRB2) and IL/2B genes. The common region of loss in these three 5q- syndrome patients includes the macrophage colony-stimulating factor-1 receptor (CSF1R), secreted protein, acidic, cysteine-rich (SPARC), and glutamate receptor (GR1A1) genes. This 5q- syndrome critical region is telomeric to and distinct from the other critical regions on 5q associated with MDS and acute myeloid leukaemia.
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PMID:Molecular cytogenetic delineation of the critical deleted region in the 5q- syndrome. 962 37

In myelodysplastic syndromes (MDS) karyotypic aberrations identify subgroups of patients with distinct clinical-morphological features and can be relevant in risk assessment of developing leukemia. Often conventional cytogenetic analysis is not sufficiently informative due to the presence of partially or completely unrecognizable chromosome markers. By chromosome microdissection (MD) and fluorescence in situ hybridization (FISH) we investigated the nature of a karyotypic marker occurring in multiple copies in one case of MDS arisen in a patient previously treated for breast cancer. Results showed dicentrics derived from telomeric fusion between interstitially deleted 20q-chromosomes. The abnormal karyotype resulted into polysomy for a deleted chromosome 20q.
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PMID:Identification of multiple copies of a 20q-chromosome in a case of myelodysplastic syndrome: a FISH study. 1022 28

Tetrasomy 8 as a sole anomaly in hematological disorders is relatively rare. To the best of our knowledge, only 19 such cases have been described in the literature to date. Of them, acute myeloid leukemia (AML) in 13 (M1, one; M2, three; M4, one; M5, eight), acute lymphoblastic leukemia(ALL) in one, myelodysplastic syndrome(MDS) in 3, polycythemia vera(PV) and myelofibrosis(MF), one case each. Their median survival was 20 weeks. Here, we report the first case of a 29-year-old man with minimally differentiated AML (AML-M0) displaying a tetrasomy 8 clone. Immunophenotyping showed positivity with CD33, CD34 and intracellular MPO, but all lymphoid markers tested were negative. Conventional cytogenetics of bone marrow cells showed 84.9% of metaphases with tetrasomy 8 in addition to 15.1% with normal diploidy. However, Fluorescence in situ hybridization(FISH) using a centromeric probe specific for chromosome 8 revealed trisomy 8 in 14.2% of interphase nuclei besides tetrasomy 8 in 82.4%. The patient died four weeks after diagnosis without therapy. In conclusion, these findings suggest that tetrasomy 8 is associated with a heterogeneous group of myeloid disorders and heralds a bad prognosis. It may be a consequence of clonal evolution of trisomy 8.
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PMID:Isolated tetrasomy 8 in minimally differentiated acute myeloid leukemia (AML-M0). 1034 86

Genomic instability induces an accumulation of genetic changes and may play a role in the pathogenesis of myelodysplastic syndromes (MDS). To clarify the possible association between genomic instability and clinical outcome in MDS patients, we compared telomere dynamics to the recently established International Prognostic Scoring System (IPSS) risk groups for MDS. We measured the terminal restriction fragments (TRFs) of 93 patients with MDS at the time of diagnosis, and telomerase activity was analyzed in 62 patients with MDS using the PCR-based telomeric repeat amplification protocol (TRAP) assay. A total of 53 of 93 MDS patients had TRFs within the age-matched normal range, and the remaining patients showed shortened TRFs (35 patients) or elongated TRFs (5 patients). MDS patients with shortened TRFs had a significantly low hemoglobin concentration (P = 0.04), a high percentage of marrow blasts (P = 0.02), and a high incidence of cytogenetic abnormalities (P < 0.05). The incidence of leukemic transformation was significantly high in patients with shortened TRF length (P < 0.05). In addition, patients with shortened TRF length were frequently seen in the IPSS high-risk group (P < 0.01). Most of the MDS patients had normal-to-low levels of telomerase activity, suggesting that changes in TRF length rather than telomerase activity may more accurately reflect the pathophysiology of MDS. MDS patients with shortened TRF length had a very poor prognosis (P < 0.01), suggesting that telomere dynamics may be linked to clinical outcome in MDS patients. Thus, an abnormal mechanism of telomere maintenance in subgroups of MDS patients may be an early indication of genomic instability. This study demonstrates that telomere stability is frequently impaired in a high-risk group of MDS patients and suggests that, in combination with the IPSS classification system, measurement of TRFs may be useful in the future to stratify MDS patients according to risk and manage the care of MDS patients.
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PMID:Telomere stability is frequently impaired in high-risk groups of patients with myelodysplastic syndromes. 1035 51

Abnormalities of chromosome band 13q14 occur in hematologic malignancies of all lineages and at all stages of differentiation. Unlike other chromosomal translocations, which are usually specific for a given lineage, the chromosomal translocation t(12;13)(p12;q14) has been observed in both B-cell and T-cell precursor acute lymphoblastic leukemia (BCP-, TCP-ALL), in differentiated and undifferentiated acute myeloblastic leukemia (AML), and in chronic myeloid leukemia (CML) at progression to blast crisis. The nature of these translocations and their pathologic consequences remain unknown. To begin to define the gene(s) involved on chromosome 13, we have performed fluorescence in situ hybridization (FISH) using a panel of YACs from the region, on a series of 10 cases of acute leukemia with t(12;13)(p12;q14) and 1 case each with "variant" translocations including t(12;13)(q21;q14), t(10;13)(q24;q14) and t(9;13)(p21;q14). In 8/13 cases/cell lines, the 13q14 break fell within a single 1.4 Mb CEPH MegaYAC. This YAC fell immediately telomeric of the forkhead (FKHR) gene, which is disrupted in the t(2;13)(q35;q14) seen in pediatric alveolar rhabdomyosarcoma. Seven of the 8 cases with breaks in this YAC were AML. In 4/13 cases, the 13q14 break fell within a 1.7-Mb YAC located about 3 Mb telomeric of the retinoblastoma (RB1) gene: all 4 cases were ALL. One case of myelodysplastic syndrome exhibited a break within 13q12, adjacent to the BRCA2 gene. These data indicate the presence of myeloid- and lymphoid-specific breakpoint cluster regions within chromosome band 13q14 in acute leukemia.
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PMID:Myeloid- and lymphoid-specific breakpoint cluster regions in chromosome band 13q14 in acute leukemia. 1037 68

In the myelodysplastic syndrome (MDS), cytogenetic abnormalities are often present and can be used as markers in studies for cell lineage involvement. Little is known of the involvement of the megakaryocytic lineage due to the variable ploidy of these cells. We applied dual-color fluorescence in situ hybridization (FISH) to routinely prepared bone marrow (BM) smears of cytogenetically normal patients and seven patients with MDS and monosomy 7 or trisomy 8. Probes specific for the centromeric regions of chromosomes 7 and 8 were detected with fluorescein isothiocyanate (FITC) and Texas Red, respectively. This enabled us to assess the ratio between the numbers of chromosomes 7 and 8 in the polyploid cells. We utilized confocal laser scanning microscopy to count the FITC and Texas Red FISH signals in the different focal layers of the megakaryocytes. Fifty-six megakaryocytes in six normal BM smears were analyzed, giving a mean ratio of 1.0, a standard deviation (SD) of 0.12, and a range of 0.8-1.33. This ratio was applied to evaluation of clonal involvement of individual megakaryocytes in the patients with MDS. In two patients with monosomy 7, the majority of the megakaryocytes were monosomic. In the five patients with trisomy 8, all or a majority of the analyzed megakaryocytes were trisomic. These results add direct evidence that in MDS megakaryocytes are involved in the malignant clone. Genes Chromosomes Cancer 25:332-338, 1999.
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PMID:Cytogenetic clonality analysis of megakaryocytes in myelodysplastic syndrome by dual-color fluorescence in situ hybridization and confocal laser scanning microscopy. 1039 26

Translocation t(11;21)(q24;q11.2) is a rare but recurrent chromosomal abnormality associated with myelodysplastic syndrome (MDS) that until now has not been characterized at the molecular level. We report here results of a molecular cytogenetic analysis of this translocation in a patient with refractory anemia. Using FISH with a panel of 11q and 21q cosmid/YAC probes, we localized the chromosome 11 breakpoint at q23.3 in a region flanked by CP-921G9 and CP-939H3 YACs, distal to the HRX/MLL locus frequently involved in acute leukemias. The chromosome 21 breakpoint was mapped in a 800-kb fragment inserted into the CP-145E3 YAC at 21q11.2, proximal to the AML1 gene. It is noteworthy that in all four cases with a t(11;21) reported until now, a second der(11)t(11;21) and loss of normal chromosome 11 could be observed either at diagnosis or during the course of the disease. Since in our case heteromorphism was detected by FISH on the centromeric region of the two der(11), the second der(11) chromosome could be the result of a mitotic recombination that had occurred on the long arm of chromosome 11, rather than of duplication of the original der(11). Constancy of secondary karyotypic changes resulting in an extra copy of the putative chimeric gene at der(11), loss of 11 qter sequences, and partial trisomy 21 suggest that neoplastic progression of MDS cases with a t(11;21) may be driven by the same mechanism(s).
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PMID:Molecular cytogenetics localizes two new breakpoints on 11q23.3 and 21q11.2 in myelodysplastic syndrome with t(11;21) translocation. 1045 99

Human acute leukemia and myelodysplasia are often associated with an interstitial deletion in chromosome arm 5q. The deleted region is hypothesized to contain tumor suppressor loci that are critical to the maintenance of normal hematopoiesis. We have identified NKIAMRE, a novel cyclin-dependent kinase-related molecule that is closely related to the rat serine/threonine kinase NKIATRE. Human NKIAMRE localizes to chromosome band 5q31.1, centromeric to the interleukin 9 locus and telomeric to IFN response factor-1. NKIAMRE was deleted at both alleles in 9 of 18 leukemic samples with chromosome band 5q31 abnormalities studied by fluorescence in situ chromosomal hybridization. NKIAMRE loss may be an important determinant of dysmyelopoiesis.
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PMID:Identification of NKIAMRE, the human homologue to the mitogen-activated protein kinase-/cyclin-dependent kinase-related protein kinase NKIATRE, and its loss in leukemic blasts with chromosome arm 5q deletion. 1046 9

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