Type of BCR-ABL Transcript Predicts Response to Imatinib Mesylate.

Imatinib Mesylate, a molecular target therapy is the first line treatment for all CML patients. We prospectively studied 50 CML patients (37 pre-treated with interferon Alfa) for response to Imatinib. Patients median age was 32 years, range, 11 to 62 years with male to female ratio being 2.5: 1. All patients were in chronic phase and received 400 mg imatinib daily for a mean time period of 18 months (range 3 to 38 months). Patients were monitored closely for clinical, hematological, cytogenetic & molecular response. Bone marrow examination was done at 3, 6, 9 then 4–6 months interval for cytogenetic response (CGR) and also for presence of BCR-ABL transcript types (b2a2, b3a2, e1a2 and e19a2) by multiplex and nested RT-PCR technique. All patients achieved complete hematological remission with in 3 months of starting Imatinib. 20/50 patients achieved Major CGR (complete -8, Partial CGR-12). Of these, 12/20(60%) patients had b2a2 transcript, 3/20 (15%) b3a2 transcript and 5/20 (25%) had both the transcripts. 24/50 had minor CGR (b2a2-10/24 (41.6%), b3a2-14/24 (58.3%). Remaining 6 patients had no Cytogenetic response (4/6-b3a2, 2/6-b2a2). Patients with BCR-ABL transcript b2a2 had a significant probability of achieving Major cytogenetic response 12/50(24%) compared with b3a2 transcripts, 3/50 (6%), p<0.001. However, there was no significant correlation between transcript type and spleen size, Hb, WBC, platelets counts. These initial observations are very provocative and suggest that site of breakpoint in major breakpoint cluster region might be predictive of cytogenetic responses to Imatinib Mesylate. We are continuing to accrue more patients in this study to confirm these results.