Contributions
Type: Publication Only
Background
Single nucleotide polymorphisms (SNPs) of multiple drug resistance (MDR1) gene are associated with altered P-glycoprotein (p-gp) activity and contribute to resistance to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML).
Aims
We aimed to demonstrate the association between MDR1 gene C3435T polymorphism and molecular response in newly diagnosed chronic phase (CP) CML patients to standard dose upfront imatinib and nilotinib therapy.
Methods
MDR1 C3435T was genotyped using polymerase chain reaction Restriction Fragment Length Polymorphisms (PCR-RFLP) at diagnosis. BCR-ABL1 transcripts level was measured by Real Time Quantitative polymerase chain reaction (RQ-PCR) at diagnosis then every 3 months.
Results
This study included 74 Philadelphia (Ph') positive CP-CML patients; 38 males and 36 females. Median age at diagnosis was 38 years (18-78). Median BCR-ABL1 level was 101%. Forty patients received imatinib (54%) while 34 received nilotinib (46%). Optimal response at 12 month was 35% in the imatinib arm versus 80% in the nilotinib arm (p=0.001). The frequency of MDR1 SNP C3435T was 46%, 32% and 22% for CC, TT and CT genotypes, respectively. Optimal response at month 12 differed significantly between imatinib and nilotinib among patients with MDR1 C3435TT genotype (11% versus 83%, respectively, p=0.002) while less significant difference was found between the two drugs in CC and CT genotypes (35% vs. 75% and 60% vs. 83%, respectively, p=0.042 & p=0.588).
Summary
MDR1 C3435TT may be used as an additional criterion for initiating nilotinib instead of imatinib as front line therapy for CP-CML patients. We demonstrated the usefulness of MDR1 SNP polymorphism in the identification of CML patients who may or may not respond optimally to imatinib.
Keyword(s): Chronic myeloid leukemia, Molecular response, SNP
Type: Publication Only
Background
Single nucleotide polymorphisms (SNPs) of multiple drug resistance (MDR1) gene are associated with altered P-glycoprotein (p-gp) activity and contribute to resistance to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML).
Aims
We aimed to demonstrate the association between MDR1 gene C3435T polymorphism and molecular response in newly diagnosed chronic phase (CP) CML patients to standard dose upfront imatinib and nilotinib therapy.
Methods
MDR1 C3435T was genotyped using polymerase chain reaction Restriction Fragment Length Polymorphisms (PCR-RFLP) at diagnosis. BCR-ABL1 transcripts level was measured by Real Time Quantitative polymerase chain reaction (RQ-PCR) at diagnosis then every 3 months.
Results
This study included 74 Philadelphia (Ph') positive CP-CML patients; 38 males and 36 females. Median age at diagnosis was 38 years (18-78). Median BCR-ABL1 level was 101%. Forty patients received imatinib (54%) while 34 received nilotinib (46%). Optimal response at 12 month was 35% in the imatinib arm versus 80% in the nilotinib arm (p=0.001). The frequency of MDR1 SNP C3435T was 46%, 32% and 22% for CC, TT and CT genotypes, respectively. Optimal response at month 12 differed significantly between imatinib and nilotinib among patients with MDR1 C3435TT genotype (11% versus 83%, respectively, p=0.002) while less significant difference was found between the two drugs in CC and CT genotypes (35% vs. 75% and 60% vs. 83%, respectively, p=0.042 & p=0.588).
Summary
MDR1 C3435TT may be used as an additional criterion for initiating nilotinib instead of imatinib as front line therapy for CP-CML patients. We demonstrated the usefulness of MDR1 SNP polymorphism in the identification of CML patients who may or may not respond optimally to imatinib.
Keyword(s): Chronic myeloid leukemia, Molecular response, SNP