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VOLUME 6 , ISSUE 2 ( April-June, 2019 ) > List of Articles

REVIEW ARTICLE

Technological Challenges for Management of Genetic Complexities of Myelodysplastic Syndromes

Bani B Ganguly, Nitin N Kadam

Keywords : Chromosomal rearrangements, Mutational complexities, Myelodysplastic syndrome, Somatic mutations, Technological challenges

Citation Information : Ganguly BB, Kadam NN. Technological Challenges for Management of Genetic Complexities of Myelodysplastic Syndromes. MGM J Med Sci 2019; 6 (2):83-89.

DOI: 10.5005/jp-journals-10036-1239

License: CC BY-NC 4.0

Published Online: 01-10-2019

Copyright Statement:  Copyright © 2019; The Author(s).


Abstract

Background: Chromosomal abnormalities (CA), including del(3q, 5q, 7q, 11q, 12p, 17p, 20q); loss of 5, 7, and Y; trisomy(8,19); i(17q); and balanced and unbalanced translocations have been demonstrated as prognostic markers in 5-tier risk-grouping and WHO-2016 classification of myelodysplastic syndromes (MDS). However, monosomal karyotype (MK) in the presence or absence of a complex karyotype (CK) has not been considered in the WHO classification. Additionally, a plethora of somatic mutations of MDS-specific and elderly populations collected through a-CGH, SNP-array, next-generation, and targeted sequencing has led to understanding of their impact on MDS-phenotype, initiation and progression of the disease, and treatment outcome in single or cooperating effects of comutations of several pathway-mechanisms. Methods: The present review on technological challenges has been raised on the information available through Google-search using MDS-genetics, mutations of MDS, diagnosis and prognosis of MDS, etc. with a view to understanding the possibilities in low-resource settings. Results: Mutual exclusivity and cross-talk of such mutations help in self-renewal of leukemic stem cells. However, molecular screening is not only time-consuming but also expensive in poor-economic settings. Nevertheless, the significance of unspecific and uncalled mutations is yet to be understood. In contrast, conventional cytogenetic assays have specific aberrations of prognostic and therapeutic values, which cover the whole genome in a cost-effective manner. However, since somatic mutations of clonal hematopoiesis of indeterminate potential (CHIP) in asymptomatic and/or patients with idiopathic cytopenia of undetermined significance (ICUS) have the potential for favoring the leukemic onset to progression, molecular screening has inherent importance within the disease-mechanism. Conclusion: The WHO-2016 risk-classification has considered mutations of SF3B1, TP53, and MLL for management of MDS, and also powered conventional cytogenetics for diagnosis and risk-stratification of MDS.

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