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

Leukemia volume 15, pages 1841–1847 (2001)Cite this article

Abstract

At diagnosis, approximately half of myelodysplastic (MDS) patients presents a normal karyotype by conventional cytogenetic analysis (CCA). Fluorescent in situhybridization (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 < 0.001) and were predictive for a worse prognosis (P < 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 = 0.0006 and 0.035, respectively). Leukemic transformation in FISH-positive patients was associated in all cases with an expansion of the abnormal clone. Our data demonstrated that a significant proportion of MDS patients with normal karyotype presented, if analyzed by FISH, clones of cytogenetically abnormal cells which played a determinant role in the progression of the disease. The presence of FISH abnormalities identified a group of MDS patients with normal karyotype characterized by an inferior prognosis.

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Acknowledgements

This work was supported by coordinated grant AIRC and MURST 60%.

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Authors and Affiliations

  1. Department of Biomedical Sciences, Section of Hematology, University of Ferrara, Corso Giovecca, 203, Ferrara, 44100, Italy

    GM Rigolin, R Bigoni, R Milani, F Cavazzini, MG Roberti, A Bardi, P Agostini, M Della Porta, A Tieghi, N Piva, A Cuneo & G Castoldi

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  1. GM Rigolin
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Rigolin, G., Bigoni, R., Milani, R. et al. Clinical importance of interphase cytogenetics detecting occult chromosome lesions in myelodysplastic syndromes with normal karyotype. Leukemia 15, 1841–1847 (2001). https://doi.org/10.1038/sj.leu.2402293

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