Assessment of BCR-ABL1 Fusion Transcripts and Their Association with Response to Imatinib Treatment in Chronic Myeloid Leukemia Patients

Abstract

Abstract Objectives: BCR-ABL1 fusion transcripts with contrasting data on response to imatinib therapy have been reported from different parts of the world. Hence, the present study aimed to determine the frequencies of transcripts and their association with response to imatinib therapy in chronic myeloid leukemia (CML) patients. Methods: A total of 170 (76 follow-up and 94 imatinib-resistant) CML samples were included in the study. BCR-ABL1 fusion transcripts and expression status were analyzed in all cases using multiplex reverse transcriptase PCyR and real-time PCyR. Sanger sequencing was used for tyrosine kinase domain (TKD) mutation screening in imatinib mesylate-resistant patients. Results: Of 170 CML patients, 36.36% showed b2a2, 63.53% had b3a2, and 2.94% had b2a2 + b3a2 isoforms. Mean platelet counts and blasts were significantly lower in b2a2 carriers (P = 0.0092; P ≤ 0.0001). Patients with b2a2 transcript were found to be more in responders group (both hematological and cytogenetic), whereas b3a2 patients were more in partial responders group and death (P = 0.763; P = 0.309). In follow-up patients, mean baseline BCR-ABL1 expression levels are significantly higher in b2a2 versus b3a2 carriers (P = 0.0351). Of 94 imatinib-resistant patients, 36 (38.29%) had acquired TKD mutations. Among 36 patients, mean BCR-ABL1 levels are significantly higher in b2a2 and b2a2 + b3a2 group (P = 0.0002; P ≤ 0.0001). TKD mutation frequency was more in b3a2 (61.11%) compared to other types. With respect to follow-up status in 36 patients, 17 patients died while 19 were on imatinib higher doses or 2nd-generation tyrosine kinase inhibitors. Of 17 patients, 41.66% had b2a2 transcript and 54.54% had b3a2 transcript. Conclusion: Patients with b3a2 transcripts might be associated with poor response and worse prognosis in CML with imatinib treatment.