Chromosomal deletions in the myelodysplastic syndrome

Mufti, Ghulam J.

doi:10.1016/0145-2126(92)90097-q

Cited by 82 publications

(22 citation statements)

References 13 publications

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“…Around 40-65% of de novo MDS patients in fact present at diagnosis a normal karyotype, whereas among secondary or therapy-related MDS the proportion of patients with normal karyotype is only 20%. [1][2][3][4][5][6][7][8] Cytogenetic data in this analysis confirmed this observation, with a figure of 48.1% of normal karyotypes in a series of 210 MDS patients observed in a 10-year period.…”

Section: Discussionsupporting

confidence: 70%

“…The biologic and clinical relevance of cytogenetic analysis in myelodysplastic syndromes (MDS) is an established acquisition [1][2][3] and karyotype has been identified by the International Prognostic Scoring System (IPSS) as one of the three variables for the definition of prognosis in MDS. 4 At diagnosis, 40 to 65% of MDS patients present normal karyotypes when assessed by conventional cytogenetic analysis (CCA) [1][2][3][4][5][6][7][8] and these patients are therefore classified, according to IPSS criteria, in the low-risk cytogenetic group.…”

Section: Introductionmentioning

confidence: 99%

“…9 The goals of this study were: (1) to evaluate by interphase FISH analysis the prevalence of the most frequent cytogenetic abnormalities in a group of MDS patients with normal karyotype; (2) to evaluate, in this subset of MDS patients, the clinical and prognostic significance of the presence of FISH abnormalities.…”

Section: Introductionmentioning

confidence: 99%

“…4 At diagnosis, 40 to 65% of MDS patients present normal karyotypes when assessed by conventional cytogenetic analysis (CCA) [1][2][3][4][5][6][7][8] and these patients are therefore classified, according to IPSS criteria, in the low-risk cytogenetic group.…”

Section: Introductionmentioning

confidence: 99%

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Clinical importance of interphase cytogenetics detecting occult chromosome lesions in myelodysplastic syndromes with normal karyotype

et al. 2001

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At diagnosis, approximately half of myelodysplastic (MDS) patients presents a normal karyotype by conventional cytogenetic analysis (CCA). Fluorescent in situ hybridization (FISH) is more sensitive than CCA allowing for the detection of minor clones and of submicroscopic lesions. We have analyzed by FISH 101 MDS patients with normal karyotype for the occurrence of the abnormalities which are most frequently observed in MDS (ie ؊5/5q؊, ؊7/7q؊, ؉8, 17p؊). In 18 patients, 15 to 32% of interphase cells were found to carry one FISH abnormality. Six patients presented trisomy 8, five had del(5)(q31), five del(7)(q31), one monosomy 7 and one del(17)(p13). FISH abnormalities were more frequently observed among patients with an increased percentage of bone marrow blasts (P ‫؍‬ 0.001). FISH abnormalities were also associated with a higher rate of progression into AML (13/18 vs 12/83, P Ͻ 0.001) and were predictive for a worse prognosis (P Ͻ 0.001). Multivariate analysis indicated that FISH positivity and IPSS risk group were independent predictors for a poor survival (P ‫؍‬ 0.0057 and 0.0123, respectively) and for leukemic transformation (P ‫؍‬

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Section: Discussionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Clinical importance of interphase cytogenetics detecting occult chromosome lesions in myelodysplastic syndromes with normal karyotype

et al. 2001

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“…[1][2][3][4] The morphologic diagnosis of MDS relies on the presence of dysplastic features and detection of clonal chromosomal abnormalities. In particular, detection of recurrent genomic lesions supports the diagnosis of a neoplastic clonal process.…”

Section: Introductionmentioning

confidence: 99%

SNP array–based karyotyping: differences and similarities between aplastic anemia and hypocellular myelodysplastic syndromes

Afable

Wlodarski

Makishima

et al. 2011

Blood

118

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In aplastic anemia (AA), contraction of the stem cell pool may result in oligoclonality, while in myelodysplastic syndromes (MDS) a single hematopoietic clone often characterized by chromosomal aberrations expands and outcompetes normal stem cells. We analyzed patients with AA (N ‫؍‬ 93) and hypocellular MDS (hMDS, N ‫؍‬ 24) using single nucleotide polymorphism arrays (SNP-A) complementing routine cytogenetics. We hypothesized that clinically important cryptic clonal aberrations may exist in some patients with BM failure. Combined metaphase and SNP-A karyotyping improved detection of chromosomal lesions: 19% and 54% of AA and hMDS cases harbored clonal abnormalities including copy-neutral loss of heterozygosity (UPD, 7%). Remarkably, lesions involving the HLA locus suggestive of clonal immune escape were found in 3 of 93 patients with AA. In hMDS, additional clonal lesions were detected in 5 (36%) of 14 patients with normal/noninformative routine cytogenetics. In a subset of AA patients studied at presentation, persistent chromosomal genomic lesions were found in 10 of 33, suggesting that the initial diagnosis may have been hMDS. Similarly, using SNP-A, earlier clonal evolution was found in 4 of 7 AA patients followed serially. In sum, our results indicate that SNP-A identify cryptic clonal genomic aberrations in AA and hMDS leading to improved distinction of these disease entities. IntroductionApproximately 10% of patients with myelodysplastic syndromes (MDS) present with a hypocellular BM and distinction of these patients from those with aplastic anemia (AA) is often a diagnostic challenge. [1][2][3][4] The morphologic diagnosis of MDS relies on the presence of dysplastic features and detection of clonal chromosomal abnormalities. In particular, detection of recurrent genomic lesions supports the diagnosis of a neoplastic clonal process. However, low cellularity of the aspirates in AA and hypocellular MDS (hMDS) often hampers precise morphologic assessment and leads to unsuccessful cytogenetic testing, resulting in misdiagnosis.Around 50% of patients with MDS, including hypocellular cases, show a normal karyotype by metaphase cytogenetics (MC), making the distinction from AA more difficult. Similarly, MDS can also develop as a late clonal complication of AA; the evolution rate of clonal chromosomal defects may be as high as 20% in 10 years, but the risk factors for evolution have not been identified. [5][6][7][8] Karyotype abnormalities encountered in this setting often include loss of chromosomes 6 and 7, and trisomy 8. 5 Identification of clonal progression is an important diagnostic task, as the prognosis of patients with AA-derived MDS is less favorable and treatment choices differ, in particular when high-risk chromosomal abnormalities are involved.Many investigators believe that the presence of chromosomal abnormalities is not compatible with the diagnosis of AA. 9,10 However, some diagnostic guidelines do not preclude a diagnosis of AA even if abnormal cytogenetics is present in otherwise hypocellular ...

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Telomere length in myelodysplastic syndromes

et al. 1997

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We have studied telomere length in the bone marrow cells or the granulocyte and lymphocyte cell fractions of 54 patients with myelodysplastic syndromes (MDS) by Southern blot hybridization using the (TTAGGG)4 probe. The average telomere length expressed as the peak telomere repeat array (TRA) in the peripheral blood, or bone marrow samples obtained from a group of 21 healthy age-matched controls (26-89 years old, mean age 55), ranged between 7.5 and 9.5 kb (mean peak TRA 8.6 kb). Twenty-four patients with refractory anemia (RA) were studied; 10/24 (42%) had telomere reduction (<7.5 kb) relative to age-matched controls and the mean peak TRA was 7.5 kb (range 4.0-9.0 kb). Eleven patients with RA with excess blasts (RAEB) were studied; 5/11 (45%) had reduced telomeres relative to age-matched controls and the mean peak TRA was 7.1 kb (range 5.0-9.0 kb). Eighteen patients with MDS in transformation to AML, comprising 15 with RAEB in transformation (RAEBt) and 3 with CMML in transformation (CMMLt), were also studied. Thirteen of eighteen patients (72%) had telomere reduction relative to age-matched controls and the mean peak TRA was 6.1 kb (range 3.5-9.0 kb). Thirty-six patients included in the study had either a normal karyotype or a simple karyotype (1 karyotypic change) and 20/36 (55%) of these had telomere reduction and the mean peak TRA was 7.1 kb (range 4.3-9.0 kb); 8 patients had a complex karyotype (3 or more karyotypic changes) and 5/8 (62%) of these had telomere reduction and the mean peak TRA was 6.1 kb (range 3.5-9.0 kb). We conclude, firstly that there is heterogeneity of telomere length in MDS and that this is observed throughout the spectrum of FAB-subtypes. Secondly, these data show that a marked reduction in telomere length in MDS if often associated with leukemic transformation and with the presence of complex karyotypic abnormalities.

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Chromosomal deletions in the myelodysplastic syndrome

Cited by 82 publications

References 13 publications

Clinical importance of interphase cytogenetics detecting occult chromosome lesions in myelodysplastic syndromes with normal karyotype

Clinical importance of interphase cytogenetics detecting occult chromosome lesions in myelodysplastic syndromes with normal karyotype

SNP array–based karyotyping: differences and similarities between aplastic anemia and hypocellular myelodysplastic syndromes

Telomere length in myelodysplastic syndromes

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