Dados do Trabalho

Título

ASSOCIATION OF THE RS12201199 POLYMORPHISM (TPMT) WITH THE RESPONSE TO IMATINIB THERAPY IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA IN PATIENTS FROM NORTHERN BRAZIL.

Introdução

Chronic Myeloid Leukemia is a proliferative disorder of myeloid cells of the hematopoietic system. The main characteristic associated with this neoplasm is the presence of the Philadelphia chromosome, which is the result of the balanced reciprocal translocation between chromosomes 9 and 22[t(9;22)(q34;q11)]. The consequence of the formation of this chromosome is the protein BCR-ABL, a constitutive and deregulated tyrosine kinase. The treatment of CML is performed with imatinib, a tyrosine kinase inhibitor, and despite being a target-specific drug, about 20% of patients do not respond well to treatment. The literature indicates that genetic variability among individuals may influence this variation in response to treatment.

Objetivo

The obective of this work was to evaluate 32 polymorphisms in drug metabolization genes in association with response to imatinib treatment in patients with CML.

Método

The sample included 168 patients diagnosed with CML treated in a reference hospital in Belém, Pará, Brazil. The study subjects were divided into two groups: patients with and without response to treatment, according to the classification used by the National Comprehensive Cancer Network. The genetic material was extracted from the peripheral blood of the patients using the DNA extraction kit BiopurKit Mini Spin Plus – 250 and was quantified using the NanoDrop 1000 spectrophotometer. The genotyping of polymorphisms was performed by real-time PCR using the QuantStudio™ 12K Flex Real-Time PCR System. And for genomic control of ancestry, a panel of 61 Ancestry Informative Markers (AIMs) was used.

Resultado

In our results, we found a statistically significant difference for the rs12201199 (A>T) polymorphism of the TPMT gene. The results show that patients with the T allele for this polymorphism are two-fold more likely to have a good response to treatment than patients with the other allele (AA vs. AT-TT; p value= 0.021141; OR= 2.62; 95% CI= 1.12 - 6.16).

Conclusão

The Thiopurine S-Methyltransferase (TPMT) gene encodes the enzyme that metabolizes thiopurine drug and the deficiency of this enzyme is associated with variability in response and toxicity in treatment with this type of drug. One study pointed out that there is variation in TPMT expression among patients who responded well or poorly to tyrosine kinase inhibitor treatment.This finding highlights the importance of the investigation of pharmacogenes to offer a more personalized treatment to cancer patients, providing a more effective treatment.

Palavras-chave

CHRONIC MYELOID LEUKEMIA, IMATINIB, TPMT, PHARMACOGENOMICS