Publications
Characteristics of BCR-ABL kinase domain mutations in chronic myeloid leukemia from India: not just missense mutations but insertions and deletions are also associated with TKI resistance
Patkar N, Ghodke K, Joshi S, Chaudhary S, Mascerhenas R, Dusseja S, Mahadik S, Gaware S, Tembhare P, Gujral S, Kabre S, Kadam-Amare P, Jain H, Dangi U, Bagal B, Khattry N, Sengar M, Arora B, Narula G, Banavali S, Menon H, Subramanian PG We document the characteristics of BCR-ABL kinase domain mutations (KDM) in the largest study from India comprising of 385 patients and demonstrate that more than half (51.9%) of these patients have detectable abnormalities in the KD both in adult and in pediatric chronic myelogenous leukemia (CML). These comprise singly occurring missense mutations (25.5%), polyclonal/compound point mutations (4.9%), and insertions/deletions (29.6%). Missense mutations were most commonly seen in the imatinib-binding region followed by the P-loop. The commonest mutation in our dataset was T315I. Other common missense mutations were Y253H, M244V, and F317L. A high prevalence of BCR-ABL exon7 deletion (p.R362fs*) was also seen (25.5% of the entire cohort), whereas the 35bpintron-derived insertion/truncation mutation detected in 12 patients. In the pediatric age group, 58.8% of patients harbored missense mutations, polyclonal/compound mutations as well as insertions and deletions. We detected 11 novel mutations (seven missense mutations and four insertions/deletions).
