BACKGROUND: Imatinib mesylate (IM) is a selective tyrosine kinase inhibitor used for treating chronic myeloid leukemia (CML). IM has high efficacy, however some individuals develop a resistance due to impaired bioavailability. Polymorphisms in genes encoding membrane transporters such as ABCB1 have been associated with differences in protein expression and function that influence the response to several drugs. AIM: To investigate the relationship of ABCB1 polymorphisms with markers of response to IM in patients with CML. METHODS: One hundred eighteen CML patients initially treated with a standard dose of IM (400mg/day) for 18months were selected at two health centers in Sao Paulo City, Brazil. The response criteria were based on the European LeukemiaNet recommendations. ABCB1 polymorphisms c.1236C>T (rs1128503), c.3435C>T (rs1045642) and c.2677G>T/A (rs2032582) were evaluated by PCR-RFLP. RESULTS: ABCB1 polymorphisms were not related with a risk for CML in this sample population (p<0.05). In the CML group, frequencies of ABCB1 SNPs were similar between responder and non-responder patients (p>0.05). In the responder group, the frequency of ABCB11236CT/2677GT/3435CT haplotype was higher in patients with major molecular response (MMR) (51.7%) than in patients without MMR (8.3%, p=0.010). Furthermore, carriers of this haplotype had increased the probability of reaching the MMR compared with the non-carriers (OR: 11.8; 95% CI: 1.43-97.3, p=0.022). CONCLUSIONS: The ABCB1 1236CT/2677GT/3435CT haplotype is positively associated with the major molecular response to IM in CML patients.
BACKGROUND:Imatinib mesylate (IM) is a selective tyrosine kinase inhibitor used for treating chronic myeloid leukemia (CML). IM has high efficacy, however some individuals develop a resistance due to impaired bioavailability. Polymorphisms in genes encoding membrane transporters such as ABCB1 have been associated with differences in protein expression and function that influence the response to several drugs. AIM: To investigate the relationship of ABCB1 polymorphisms with markers of response to IM in patients with CML. METHODS: One hundred eighteen CMLpatients initially treated with a standard dose of IM (400mg/day) for 18months were selected at two health centers in Sao Paulo City, Brazil. The response criteria were based on the European LeukemiaNet recommendations. ABCB1 polymorphisms c.1236C>T (rs1128503), c.3435C>T (rs1045642) and c.2677G>T/A (rs2032582) were evaluated by PCR-RFLP. RESULTS:ABCB1 polymorphisms were not related with a risk for CML in this sample population (p<0.05). In the CML group, frequencies of ABCB1 SNPs were similar between responder and non-responder patients (p>0.05). In the responder group, the frequency of ABCB11236CT/2677GT/3435CT haplotype was higher in patients with major molecular response (MMR) (51.7%) than in patients without MMR (8.3%, p=0.010). Furthermore, carriers of this haplotype had increased the probability of reaching the MMR compared with the non-carriers (OR: 11.8; 95% CI: 1.43-97.3, p=0.022). CONCLUSIONS: The ABCB1 1236CT/2677GT/3435CT haplotype is positively associated with the major molecular response to IM in CMLpatients.
Authors: Joel L Weissfeld; Brenda Diergaarde; Tomoko Nukui; Shama Buch; Arjun Pennathur; Mark A Socinski; Jill M Siegfried; Marjorie Romkes Journal: J Thorac Oncol Date: 2014-09 Impact factor: 15.609
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Authors: Douglas Vivona; Luciene Terezina Lima; Alice Cristina Rodrigues; Carolina Tosin Bueno; Greyce Kelly Steinhorst Alcantara; Luiza Saldanha Ribeiro Barros; Vania Tiestsche DE Moraes Hungria; Carlos Sérgio Chiattone; Maria DE Lourdes Lopes Ferrari Chauffaille; Elvira Maria Guerra-Shinohara Journal: Oncol Lett Date: 2014-02-07 Impact factor: 2.967