Authors: Leena Rawal , . Vamshi Krishna Thamtam , Sindhu Prabhash , Shiba Ranjan Mishra , Ravinder Kumar , Sumit Jangra , Reena Nakra , Vandana Lal

Abstract

Background: The BCR::ABL1 gene fusion is the hallmark of chronic myeloid leukemia (CML). Variant Philadelphia chromosome (Ph)-positive cases with complex chromosomal rearrangements involving additional chromosomes occur in 4-11% of c ases, but their prognostic significance remains unclear.

Methods: A 20-year-old male presenting with leukocytosis and anemia was evaluated using conventional
cytogenetics, fluorescence in situ hybridization (FISH), and reverse transcription PCR (RT-PCR) to identify chromosomal abnormalities and BCR::ABL1 transcript type.

Results: Cytogenetic analysis revealed a novel balanced five-way translocation: 46,XY,t(9;10;15;21;22)
(q34;p11.2;q22;q22;q11.2). FISH confirmed the BCR::ABL1 fusion in 97% of nuclei, and RT-PCR detected the
e13a2 (p210) BCR::ABL1 transcript. The patient exhibited rapid progression to blast crisis and resistance to
first-line imatinib therapy.

Conclusion: This novel five-way translocation in Ph-positive CML highlights the importance of comprehensive
cytogenetic and molecular characterization to detect rare variants that may influence treatment response and
prognosis.

Keywords: Chronic myeloid leukemia (CML); BCR::ABL1 fusion; Philadelphia chromosome; Five-way translocation; Cytogenetics