C1236T polymorphism in MDR1 gene correlates with therapeutic response to imatinib mesylate in Indian patients with chronic myeloid leukaemia.
Patients with chronic myeloid leukaemia show an excellent response to treatment with imatinib. However, in some patients, the disease is resistant to imatinib. This resistance may be related to the presence of genetic variations on the drug's pharmacokinetics and metabolism. We therefore studied three polymorphisms (C1236T, G2677T and C3435T) in the human multidrug-resistance gene (MDR1) in 86 patients with chronic myeloid leukaemia treated with imatinib. Imatinib resistance was more frequent in patients with TT genotype at locus 1236 than in those with CT/CC genotypes (p=0.003). For the other two loci (G2677T and C3435T), resistance was seen to be higher for TT genotype when compared to GG/GT and CT/CC but it was not statistically significant (p=0.13 and p=0.099). In conclusion, determination of C1236T MDR1 genotype may help to predict response to imatinib therapy in patients with chronic myeloid leukaemia.
Department of Haematology, All India Institute of Medical Sciences, New Delhi 110029, India.
Sunita
S
Chhikara
Department of Haematology, All India Institute of Medical Sciences, New Delhi 110029, India.
Sudha
S
Sazawal
Department of Haematology, All India Institute of Medical Sciences, New Delhi 110029, India.
Pravas
P
Mishra
Department of Haematology, All India Institute of Medical Sciences, New Delhi 110029, India.
Rekha
R
Chaubey
Department of Haematology, All India Institute of Medical Sciences, New Delhi 110029, India.
Manoranjan
M
Mahapatra
Department of Haematology, All India Institute of Medical Sciences, New Delhi 110029, India, renusaxena@outlook.com.
Renu
R
Saxena
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use*; D007194:India; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D000068877:Imatinib Mesylate