Investigating Breakpoint Cluster Region-Abelson 1(BCR-ABL) (BCRABL1) signal patterns across chronic myeloid leukemia morphologic phases and its impact on molecular response

Objectives: For the diagnosis of chronic myeloid leukemia (CML) FISH test confirms the presence of BCR-ABL translocation in CML. It also shows whether the signal pattern is typical or atypical. CML has to be monitored through quantitative real time polymerase chain reaction(qRT-PCR) for Breakpoint Cluster Region-Abelson 1(BCR-ABL1) transcripts to evaluate the achievement of major molecular response (MMR). However, the significance of the association of atypical signal patterns with major molecular response (MMR) achievement remains to be studied. Material and Methods: In all newly diagnosed cases of CML, peripheral blood, bone marrow examination, European treatment and outcome study score(EUTOS) score assessment, FISH and real time polymerase chain reaction(RT-PCR) were performed. Results: Among 369 CML cases, 70 (19%) cases of blast crisis and 299 (81%) cases of chronic phase were reported. Among these 299 cases presenting with chronic myeloid leukemia - chronic phase (CML-CP) on bone marrow biopsy, increased fibrosis was noted in 29 (9.7%) cases. On FISH, atypical patterns were present in 57.4% cases of chronic myeloid leukemia-blast crisis (CML-BC), 65.5% of CML with fibrosis, and 29.6% cases of CML-CP. RTPCR after one year of therapy showed MMR in 62.9% of cases who had a typical signal pattern on FISH, whereas the number dropped to a mere 7.9% in patients with an atypical pattern on FISH. Independent of EUTOS risk stratification, CML-CP cases with atypical FISH patterns showed a significant difference in the attainment of MMR compared to CML-CP cases with typical patterns (9.1% vs 65.9%). Conclusion: Ours is one of the few studies that analyzed and compared FISH patterns with morphological diagnosis and MMR status on RT-qPCR in such a large cohort of patients with CML CML BC and CML-CP with fibrosis cases significantly show more atypical patterns compared to CML-CP cases. Also, cases with atypical patterns attained MMR significantly in fewer numbers compared to cases with typical patterns. Hence FISH test with emphasis on atypical patterns can also be considered for the prognostication of patients with CML.