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Evaluation of molecular response and expression of ABCF2, ALOX15B, PAWR, ncFOXO3A, ncMYLIP and ncSLC44A2 genes in patients with chronic myeloid leukemia treated with second generation tyrosine kinase inhibitors

Grant number: 13/05713-5
Support type:Scholarships in Brazil - Master
Effective date (Start): July 01, 2013
Effective date (End): June 30, 2015
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal researcher:Katia Borgia Barbosa Pagnano
Grantee:Beatriz Felicio Ribeiro
Home Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil


Chronic myeloid leukemia (CML) is a chronic myeloproliferative disorder characterized by the presence of Philadelphia (Ph) and production of the BCR-ABL fusion protein, with constitutive tyrosine kinase activity. Imatinib is currently the first line treatment approved for CML in Brazil. In spite of high response rates, some patients are resistant or intolerant to treatment, and need to switch treatment to second or third generation tyrosine kinase inhibitors (TKI) and eventually bone marrow transplantation. Resistance mechanisms include point mutations in the BCR-ABL kinase domain, amplification, low drug influx and activation of alternative oncogenic pathways. Recently our group described several differentially expressed genes in patients responsive and non-responsive to dasatinib, detected by microarrays analysis. The aim of this study is to evaluate molecular response by measuring BCR-ABL levels by quantitative RT-PCR (PCR-Q) in patients resistant and/or intolerant to imatinib, using second or third line TKIs. BCR-ABL transcript levels measured in different time points of the treatment will be correlated with cytogenetic response, overall survival and event-free survival. Gene expression of genes related to dasatinib response (ncMYLIP, ncSLC4A2, ncFOXO3A, ALOX15B, ABCF2 and PAWR) will be analyzed by RQ-PCR, in patients resistant or responsive to dasatinib. The analysis of genes related to response to dasatinib may help to understand resistance mechanisms and in developing future therapies.

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