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

• Main Authors: 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
• Format: Article
• Language: English
• Published: PAGEPress Publications 2018-01-01
• Series: Mediterranean Journal of Hematology and Infectious Diseases
• Subjects: Acute promyelocytic leukemia molecular subtypes in India, variant APL, PLZF-RARA, rare translocations of APL
• Online Access: https://www.mjhid.org/index.php/mjhid/article/view/3115

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