Chromosomal mutations of hematologic malignancies of the elderly: Chromosomal aberrations of indeterminate potential in MIC-exposed Bhopal population

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Bani Bandana Ganguly, Shouvik Mandal and Nalok Banerjee

MGM New Bombay Hospital, India
National Institute for Research in Environmental Health, India

: J Forensic Toxicol Pharmacol

Abstract

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Numerical and structural alterations in human chromosomes indicate exposure to chemicals/radiation, heritable congenital disorders and acquired malignancies. Hematologic malignancies are diagnosed and prognosticated based on the chromosomes involved and complexity of rearrangements. Acquisition of mutations of genes and chromosomes due to biological senescence among elderly results in foundation of clonal abnormalities of indeterminate potential, which is agitated further by other cooperating mutations for neoplastic patho-mechanism. Myelodysplastic syndrome (MDS) has been characterized with pre-malignant hematopoietic changes causing blood cytopenia and marrow dysplasia in ~18.4% elderly of ~65 years median age with a high risk of acute leukemia. Predominantly del/-(5, 7), trisomy 8, del(20q), -Y as single or in combination with complex rearrangements indicate severity of the disease and risk of transformation. Conventional cytogenetic analysis in bone marrow of the cytopenic elderly and peripheral blood of the methyl isocyante (MIC)-exposed Bhopal people revealed multiple clonal abnormalities, which may indicate early onset of hematopoietic disorder in the MICexposed people. Chromosomal aberrations (CA) detected in stimulated blood-lymphocytes may represent cytogenetic CHIP (clonal hematopoiesis of indeterminate potential) and warrants marrow-cytogenetics for screening of specific mutations. MICexposed Bhopal people are aged ~60 years or more 30 years post-disaster and presented with blood cytopenia. However, multiples of environmental and occupational confounders might have cooperated with their life- style/tobacco consumption for yielding chromosomal damage as a result of gene-environment interaction. Therefore, it is not apparent that MICexposure is the sole cause of such chromosomal rearrangements, even after adjustment of initial level of damage measured immediately after the accident. However, ascertainment of CA is essential in bone marrow of those selective individuals of Bhopal for detection of clonal aberrations and early therapeutic intervention. Since mRNA splicing and epigenetic mutations are demonstrated as founder mutation of MDS, screening of gene mutations of several functions in MIC-exposed population may direct re-understanding of disease mechanism and tailoring targeted drugs for such exposure/population.

Biography

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Email: mgmgeneticlab@yahoo.com