MOLECULAR HETEROGENEITY IN ACUTE PROMYELOCYTIC LEUKEMIA - A SINGLE CENTRE EXPERIENCE FROM INDIA

Main Article Content

Nikhil Rabade
Goutham Raval
Shruti Chaudhary
PG Subramanian
Rohan Kodgule
Swapnali Joshi
Prashant Tembhare
Hasmukh Jain
Manju Sengar
Syed Hasan K
Pratibha Amare Kadam
Dhanalaxmi Shetty
Gaurav Narula
Shripad Banavali
Sumeet Gujral
Nikhil Patkar

Keywords

Acute promyelocytic leukemia molecular subtypes in India, variant APL, PLZF-RARA, rare translocations of APL

Abstract

Atypical breakpoints and variant APL cases involving alternative chromosomal aberrations are seen in a small subset of acute promyelocytic leukemia (APL) patients. Over 7 different partner genes for RARA have been described. Although rare, these variants prove to be a diagnostic challenge and require combination of advanced cytogenetic and molecular techniques for accurate characterization. Heterogeneity occurs not only at the molecular level but also at clinico-pathological level influencing treatment response and outcome. In this case series we describe the molecular heterogeneity of APL seen in a single tertiary referral centre with a focus on seven variant APL cases from a single tertiary cancer center in India over a period of two and a half years. We discuss five cases with PLZF-RARA fusion and two novel PML-RARA variants, including a Bcr3 variant involving fusion of PML exon4 and RARA exon3 with an additional 40 nucleotides originating from RARA intron2, another involving exon 6 of PML and exon 3 of RARA with addition of 126 nucleotides, which mapped to the central portion of RARA intron 2  To the best of our knowledge this is the first of kind case series from India

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