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CC BY 4.0 · Indian J Med Paediatr Oncol 2023; 44(05): 482-493
DOI: 10.1055/s-0043-1766133
Review Article

Role of Cytogenetics and FISH in Laboratory Workup of B Cell Precursor Acute Lymphoblastic Leukemia

Aaishwarya Dhabe
1   Department of Cytogenetics, Tata Medical Center, MAR(EW), Newtown, Kolkata, West Bengal, India
,
Rubina Islam
2   Tata Translation Cancer Research Center, Tata Medical Center, MAR(EW), Newtown, Kolkata, West Bengal, India
,
Karthik Ramakrishnan
1   Department of Cytogenetics, Tata Medical Center, MAR(EW), Newtown, Kolkata, West Bengal, India
,
Mayur Parihar
1   Department of Cytogenetics, Tata Medical Center, MAR(EW), Newtown, Kolkata, West Bengal, India
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Abstract

Modern therapeutic protocols in acute leukemias risk stratify disease based on genetic characterization of the neoplastic cells and their response to treatment. Genetic characterization is routinely performed by cytogenetic testing of leukemic cells and is a standard component of modern risk-adapted therapy in acute lymphoblastic leukemia (ALL). High-throughput technologies like RNA sequencing have identified multiple novel subtypes in recent years. The cytogenetic strategy using GTG and fluorescent in-situ hybridization (FISH) has to be adapted to identify not only the primary principal chromosomal abnormalities but also the novel subtypes. In the review, we describe a systematic comprehensive cytogenetic strategy that integrates information from immunophenotyping, flow-based DNA ploidy, and karyotyping complemented by targeted FISH studies to identify more than 70% of genetic abnormalities described in B cell precursor ALL. The simplified strategy includes a four-probe FISH and flow ploidy strategy, ± karyotyping that identifies high risk (KMT2A, BCR::ABL1, hypodiploidy, iAMP21) and standard risk (ETV6::RUNX1 and high hyperdiploid) cytogenetic groups. The extended FISH panel includes probes targeting MEF2D, ZNF384, and CRLF2 rearrangements that are used intuitively on integrating the immunophenotyping features that characterize these entities. The strategy also includes a systematic approach to identify masked hypodiploidy integrating targeted FISH analysis directed toward identifying monosomies of chromosomes 7, 15, and 17 and flow cytometry-based DNA ploidy analysis. The recently described PH-like ALL is characterized by ABL class fusions and rearrangements of CRLF2 and JAK2 genes. FISH analysis using break-apart probes can be used to identify these aberrations. The cytogenetic approach also includes FISH analysis to identify intragenic and whole gene deletions of the IKZF1 genes that identify a subset of patients associated with high risk of treatment failure.

Keywords

acute lymphoblastic leukemia - ETV6::RUNX1 fusion - hyperdiploidy - BCR::ABL1 fusion - KMT2A gene rearrangement - iAMP21 - FISH in ALL - karyotyping

Authors' Contributions

R.I. and M.P. wrote the original draft, K.R., A.D. collated the data and figures; M.P. and R.I. have full access to all data and the final responsibility for publication. All authors reviewed the manuscript draft submitted for publication.




Publication History

Article published online:
17 April 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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