Molecular Heterogeneity in Acute Promyelocytic Leukemia - a Single Center Experience from India

Atypical breakpoints and variant APL cases involving alternative chromosomal aberrations are seen in a small subset of acute promyelocytic leukemia (APL) patients. Over seven different partner genes for RARA have been described. Although rare, these variants prove to be a diagnostic challenge and require a 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 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 fusion and two novel variants, including a Bcr3 variant involving fusion of exon4 and exon3 with an additional 40 nucleotides originating from intron2, another involving exon 6 of and exon 3 of with addition of 126 nucleotides, which mapped to the central portion of intron 2. To the best of our knowledge, this is the first case series of this kind from India.