BCR::ABL1 major (p210) IS, Quantitative (LAB9762) and BCR::ABL1 t(9;22) minor (p190), Quantitative (LAB7547)

FISH is recommended for diagnosis purposes or when the BCR::ABL1 isoform is unknown and PCR is the test of choice for monitoring a known BCR::ABL1 isoform

Clinical Background
  • The BCR::ABL1 fusion gene results from a reciprocal translocation between chromosome 9 and chromosome 22. This genetic rearrangement is commonly found in hematologic malignancies, particularly in patients with chronic myeloid leukemia (CML), as well as in subsets of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) cases. 
  • There are distinct BCR::ABL1 fusion transcripts that produce variously sized fusion proteins depending on the translocation breakpoints. The most common breakpoint occurs in the major BCR region, leading to the production of the p210 protein. Less frequently, breakpoints occur in the minor BCR region, resulting in a shorter transcript that encodes the p190 protein. 
  • Molecular testing is a crucial component for diagnosing and monitoring certain hematologic malignancies. Two primary methods utilized in this process are fluorescence in situ hybridization (FISH) and real-time quantitative polymerase chain reaction (PCR).
Common Pitfalls
  • PCR assays are designed to detect BCR::ABL1 isoforms, specifically the p190 and p210 variants. However, due to this focus, these standard assays may produce false-negative results by failing to identify rare BCR::ABL1 isoforms. 
Key Takeaways
  • FISH is recommended for diagnosis and for unknown BCR::ABL1 isoforms. 
  • PCR is the test of choice for monitoring. 
  • Once FISH is positive for the rearrangement during diagnosis, a PCR test can be performed to identify the isoform. 
References
  1. Adnan-Awad S, Kim D, Hohtari H, et al. Characterization of p190-Bcr-Abl chronic myeloid leukemia reveals specific signaling pathways and therapeutic targets. Leukemia. 2021;35(7):1964-1975. doi:10.1038/s41375-020-01082-4. 
  2. Amarante-Mendes GP, Rana A, Datoguia TS, Hamerschlak N, Brumatti G. BCR-ABL1 Tyrosine Kinase Complex Signaling Transduction: Challenges to Overcome Resistance in Chronic Myeloid Leukemia. Pharmaceutics. 2022;14(1):215. Published 2022 Jan 17. doi:10.3390/pharmaceutics14010215. 

Written By: Ana Villanueva, MD and Patricia Hernandez, MD

Reviewed By: Bijal Parikh, MD PhD

Last Edited: 2025-02-10

Last Reviewed: 2025-02-10