Download PDF
CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2021; 42(03): 261-267
DOI: 10.1055/s-0041-1733827
Original Article

Study of the Chromosomal Abnormalities and Associated Complex Karyotypes in Hematological Cancer in the Population of West Bengal: A Prospective Observational Study

Puspal De
1   Department of Genetics, Institute of Genetic Engineering, Kolkata, West Bengal, India
,
Madhumitha J Mukhopadhyay
1   Department of Genetics, Institute of Genetic Engineering, Kolkata, West Bengal, India
› Author Affiliations Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. All the research work done by the affiliated institution funding.
› Further Information
   Permissions and Reprints

Abstract

Introduction Chromosomal instability is an important feature of hematological cancer. The pathogenesis is complex and it involves genetic and epigenetic factors. As a genetic factor, chromosomal instability may play a key role in leukemogenesis. Accumulation of genetic alteration is mainly responsible for numerical and structural chromosomal rearrangement or clonal evaluation. But disease progression is often driven by chromosomal translocation, hyper- or hypodiploidy with structural abnormalities, and complex karyotypes.

Objective This research aimed to study the different types of chromosomal abnormalities in clinically suspected hematological cancer patients.

Materials and Methods Cytogenetic analysis was performed based on phytohemaglutinin stimulated peripheral blood lymphocyte cultures and bone marrow culture, without mitogen, of the respective patients of West Bengal from March 2016 to February 2018. All clinically suspected hematological cancer patients referred for karyotyping to the institutional genetics department have been included without any biasness of sex and age. Karyotypes were described according to the International System for Cytogenetic Nomenclature (ISCN 2005).

Results In the present study, 56 clinically suspected hematological cancer cases were observed and 41 cases of chromosomal rearrangement were found which clearly show chromosomal instability as the main driving force for hematological cancer transformation. Presence of variant Philadelphia chromosomes with classical translocation, mosaic complex karyotypes, variable numerical, and structural chromosomal abnormality, along with severe-to-moderate hypo- and hyperdiploidy, and presence of marker chromosomes were the main findings of this study.

Conclusion The result shows that the detection of chromosomal instability was important for preliminary diagnosis, treatment, prognosis, and further management. So the present study provided additional information about chromosomal instability in hematological cancer at Kolkata and adjoining regions.

Keywords

chromosomal instability - hematological cancer - complex karyotype - leukocyte culture


Publication History

Article published online:
20 September 2021

© 2021. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Thieme Medical and Scientific Publishers Private Ltd.
A-12, Second Floor, Sector -2, NOIDA -201301, India

 

  • Reference

  • 1 Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100 (01) 57-70
    CrossrefPubMedGoogle Scholar
  • 2 Diaz-Cano SJ. Tumor heterogeneity: mechanisms and bases for a reliable application of molecular marker design. Int J Mol Sci 2012; 13 (02) 1951-2011
    CrossrefPubMedGoogle Scholar
  • 3 Bhatt AN, Mathur R, Farooque A, Verma A, Dwarakanath BS. Cancer biomarkers - current perspectives. Indian J Med Res 2010; 132: 129-149
    PubMedGoogle Scholar
  • 4 Garnis C, Buys TPH, Lam WL. Genetic alteration and gene expression modulation during cancer progression. Mol Cancer 2004; 3: 9
    CrossrefPubMedGoogle Scholar
  • 5 Vayen B, Thomay K, Schlbelberger B. Induction of chromosomal instability via Telomer dysfunction and epigenetic alteration in myeloid neoplasia. Cancer 2013; 5 (03) 857-874
    Google Scholar
  • 6 Rowe JM. Prognostic factors in adult acute lymphoblastic leukaemia. Br J Haematol 2010; 150 (04) 389-405
    CrossrefPubMedGoogle Scholar
  • 7 Silva ML, Ornellas de Souza MH, Ribeiro RC. et al Cytogenetic analysis of 100 consecutive newly diagnosed cases of acute lymphoblastic leukemia in Rio de Janeiro. Cancer Genet Cytogenet 2002; 137 (02) 85-90
    CrossrefPubMedGoogle Scholar
  • 8 Moorhead PS, Nowell PC, Mellman WJ, Battips DM, Hungerford DA. Chromosome preparations of leukocytes cultured from human peripheral blood. Exp Cell Res 1960; 20: 613-616
    CrossrefPubMedGoogle Scholar
  • 9 Seabright M. A rapid banding technique for human chromosomes. Lancet 1971; 2 (7731) 971-972
    CrossrefPubMedGoogle Scholar
  • 10 World Health Organization. World Cancer Report 2014. Switzerland: World Health Organization; 2014
    CrossrefGoogle Scholar
  • 11 Graux C. Biology of acute lymphoblastic leukemia (ALL): clinical and therapeutic relevance. Transfus Apheresis Sci 2011; 44 (02) 183-189
    CrossrefPubMedGoogle Scholar
  • 12 Alcalay M, Orleth A, Sebastiani C. et al Common themes in the pathogenesis of acute myeloid leukemia. Oncogene 2001; 20 (40) 5680-5694
    CrossrefPubMedGoogle Scholar
  • 13 Cheson BD, Bennett JM, Grever M. et al National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood 1996; 87 (12) 4990-4997
    CrossrefPubMedGoogle Scholar
  • 14 Pasternak G, Hochhaus A, Schultheis B, Hehlmann R. Chronic myelogenous leukemia: molecular and cellular aspects. J Cancer Res Clin Oncol 1998; 124 (12) 643-660
    CrossrefPubMedGoogle Scholar
  • 15 Patnaik MM, Tefferi A. Chronic myelomonocytic leukemia: 2018 update on diagnosis, risk stratification and management. Am J Hematol 2018; 93 (06) 824-840
    CrossrefPubMedGoogle Scholar
  • 16 McCullough KB, Patnaik MM. Chronic myelomonocytic leukemia: a genetic and clinical update. Curr Hematol Malig Rep 2015; 10 (03) 292-302
    CrossrefPubMedGoogle Scholar
  • 17 Fisher AM, Strike P, Scott C, Moorman AV. Breakpoints of variant 9;22 translocations in chronic myeloid leukemia locate preferentially in the CG-richest regions of the genome. Genes Chromosomes Cancer 2005; 43 (04) 383-389
    CrossrefPubMedGoogle Scholar
  • 18 Chauffaille ML. Cytogenetics and FISH monitoring CMLduring tyrosine kinase inhibitors treatment. Rev Bras Hematol Hemoter 2008; 30 (01) 13-19
    Google Scholar
  • 19 Yehuda O, Abeliovich D, Ben-Neriah S. et al Clinical implications of fluorescence in situ hybridization analysis in 13 chronic myeloid leukemia cases: Ph-negative and variant Ph-positive. Cancer Genet Cytogenet 1999; 114 (02) 100-107
    CrossrefPubMedGoogle Scholar
  • 20 Kelman Z, Prokocimer M, Peller S. et al Rearrangements in the p53 gene in Philadelphia chromosome positive chronic myelogenous leukemia. Blood 1989; 74 (07) 2318-2324
    CrossrefPubMedGoogle Scholar
  • 21 Huret JL, Ahmad M, Arsaban M. et al Atlas of genetics and cytogenetics in oncology and haematology in 2013. Nucleic Acids Res 2013; 41 (Database issue) D920-D924
    CrossrefPubMedGoogle Scholar
  • 22 Amare P, Gladstone B, Varghese C, Pai S, Advani S. Clinical significance of cytogenetic findings at diagnosis and in remission in childhood and adult acute lymphoblastic leukemia: experience from India. Cancer Genet Cytogenet 1999; 110 (01) 44-53
    CrossrefPubMedGoogle Scholar
  • 23 Panzer-Grümayer ER, Fasching K, Panzer S. et al Nondisjunction of chromosomes leading to hyperdiploid childhood B-cell precursor acute lymphoblastic leukemia is an early event during leukemogenesis. Blood 2002; 100 (01) 347-349
    CrossrefPubMedGoogle Scholar
  • 24 Bovery T. Concerning the origin of malignant tumor by TheoderBoveri. J Cell Sci 2008; 121: 1-84
    CrossrefPubMedGoogle Scholar
  • 25 Negrini S, Gorgoulis VG, Halazonetis TD. Genomic instability–an evolving hallmark of cancer. Nat Rev Mol Cell Biol 2010; 11 (03) 220-228
    CrossrefPubMedGoogle Scholar
  • 26 Jallepalli PV, Lengauer C. Chromosome segregation and cancer: cutting through the mystery. Nat Rev Cancer 2001; 1 (02) 109-117
    CrossrefPubMedGoogle Scholar
  • 27 Santaguida S, Amon A. Short- and long-term effects of chromosome mis-segregation and aneuploidy. Nat Rev Mol Cell Biol 2015; 16 (08) 473-485
    CrossrefPubMedGoogle Scholar
  • 28 Holland AJ, Cleveland DW. Losing balance: the origin and impact of aneuploidy in cancer. EMBO Rep 2012; 13 (06) 501-514
    CrossrefPubMedGoogle Scholar
  • 29 Ito C, Kumagai M, Manabe A. et al Hyperdiploid acute lymphoblastic leukemia with 51 to 65 chromosomes: a distinct biological entity with a marked propensity to undergo apoptosis. Blood 1999; 93 (01) 315-320
    CrossrefPubMedGoogle Scholar
  • 30 Hiroyuki T, Ichiro M, Yasuhiko K. Why does childhood acut lymphoblastic leukemia with hyperdiploidy show a fevour prognosis?. Cancer Genet 1990; 50 (02) 273-275
    CrossrefPubMedGoogle Scholar
  • 31 Bloomfield CD, Goldman AI, Alimena G. et al Chromosomal abnormalities identify high-risk and low-risk patients with acute lymphoblastic leukemia. Blood 1986; 67 (02) 415-420
    CrossrefPubMedGoogle Scholar
  • 32 Pui CH, Williams DL, Roberson PK. et al Correlation of karyotype and immunophenotype in childhood acute lymphoblastic leukemia. J Clin Oncol 1988; 6 (01) 56-61
    CrossrefPubMedGoogle Scholar
  • 33 Fenaux P, Lai JL, Morel P. et al Cytogenetics and their prognostic value in childhood and adult acute lymphoblastic leukemia (ALL) excluding L3. Hematol Oncol 1989; 7 (04) 307-317
    CrossrefPubMedGoogle Scholar
  • 34 Look AT, Roberson PK, Williams DL. et al Prognostic importance of blast cell DNA content in childhood acute lymphoblastic leukemia. Blood 1985; 65 (05) 1079-1086
    CrossrefPubMedGoogle Scholar
  • 35 Smets LA, Homan-Blok J, Hart A. et al Prognostic implication of hyperdiploidy as based on DNA flow cytometric measurement in childhood acute lymphocytic leukemia–a multicenter study. Leukemia 1987; 1 (03) 163-166
    PubMedGoogle Scholar
  • 36 Zemanova Z, Michalova K, Sindelarova L. et al Prognostic value of structural chromosomal rearrangements and small cell clones with high hyperdiploidy in children with acute lymphoblastic leukemia. Leuk Res 2005; 29 (03) 273-281
    CrossrefPubMedGoogle Scholar
  • 37 Debatin KM, Stahnke K, Fulda S. Apoptosis in hematological disorders. Semin Cancer Biol 2003; 13 (02) 149-158
    CrossrefPubMedGoogle Scholar