LETTER TO THE EDITOR Spectrum of BCR-ABL kinase domain mutations in patients with chronic myeloid leukemia from India with suspected resistance to imatinib-mutations are rare and have different distributions PREETHA MARKOSE 1 , EZHILARASI CHENDAMARAI 1 , POONKUZHALI BALASUBRAMANIAN 1 , SHAJI RAMACHANDRAN VELAYUDHAN 1 , VIVI M. SRIVASTAVA 2 , VIKRAM MATHEWS 1 , BIJU GEORGE 1 , AURO VISWABANDYA 1 , ALOK SRIVASTAVA 1 , & MAMMEN CHANDY 1 1 Department of Haematology and 2 Cytogenetics Unit, Christian Medical College, Vellore, India (Received 2 July 2009; revised 7 September 2009; accepted 12 September 2009) The introduction of tyrosine kinase inhibitors has revolutionized the treatment of chronic myeloid leukemia (CML). Imatinib mesylate, which compe- titively targets the adenosine 5-triphosphate (ATP)- binding site of the kinase domain of BCR-ABL [1] is now the first choice of therapy for CML. The incidence of CML in India varies from 0.8 to 2.2 and 0.6 to 1.6 per 100 000 population in males and females, respectively. The overall incidence of CML is 42.1% of all the adult leukemias as seen in our outpatient department from the year 1997 to 2008 (1226 out of 2975 adult leukemias). Despite the impressive rate of complete hematological response and complete cytogenetic remissions, some cases show primary or secondary resistance to imatinib. Several mechanisms have been attributed as the cause for clinical resistance to imatinib [2,3]. Among these, point mutations in the BCR-ABL kinase domain appear to be the most common mechanism occurring in 30–90% of patients who develop resistance [4,5]. A point mutation in BCR-ABL kinase domain can cause an amino acid change and impair imatinib binding by interrupting the critical contact point or by altering the conformation of the protein [6]. To date, more than 50 different kinase domain mutations have been identified and they confer different degrees of in vitro resistance to imatinib. There have been very few reports on the spectrum of BCR-ABL kinase domain mutations in Asian patients with CML [7–9]. In a recent study from the Korean population, CML patients with imatinib resistance showed high rates (63%) of mutations in the BCR-ABL kinase domain [7]. Since the response rate to imatinib is suboptimal in the Indian population [10,11], it is possible that this can be attributed to a different mutation spectrum in this population. The aim of the present study was therefore to analyze the frequency and the spectrum of BCR-ABL kinase domain mutations in Indian patients with CML with clinical resistance to imatinib. Between January 2004 and January 2009, periph- eral blood samples were collected from 76 patients with CML with suspected clinical resistance to imatinib diagnosed in different phases of the disease (54 in chronic phase, 14 in accelerated phase, and 8 in blast crisis). Eligible patients visiting the outpatient clinic at the department of Haematology, Christian Medical College, Vellore were enrolled in the Glivec (imatinib) International Patient Assistance Program (GIPAP). Patients with CML in the chronic phase, accelerated phase, and blast crisis stage received standard doses of 400, 600, and 800 mg/day of imatinib, respectively. Primary resistance to imatinib was defined as failure to achieve hematological remission within 3– 6 months or failure to achieve any level of cytogenetic response at 6 months, major cytogenetic response at 12 months, or complete cytogenetic response at 18 months. Secondary resistance was defined as relapse Correspondence: Poonkuzhali Balasubramanian, Ph.D., Associate Professor, Department of Haematology, Christian Medical College, Vellore 632004, India. Tel: þ91-416-2283476. Fax: þ91-416-2226449. E-mail: bpoonkuzhali@cmcvellore.ac.in Leukemia & Lymphoma, December 2009; 50(12): 2092–2095 ISSN 1042-8194 print/ISSN 1029-2403 online Ó 2009 Informa Healthcare USA, Inc. DOI: 10.3109/10428190903332486 Leuk Lymphoma Downloaded from informahealthcare.com by Washington University Library on 04/20/15 For personal use only.