Identification of target genes using gene expression profile of granulocytes from patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors

Autor(es)

Mascarenhas, Cintia do Couto ^[1] ; da Cunha, Anderson Ferreira ^[2] ; Brugnerotto, Ana Flavia ^[1] ; Gambero, Sheley ^[1] ; de Almeida, Maria Helena ^[1] ; Carazzolle, Marcelo F. ^[3] ; Barbosa Pagnano, Katia Borgia ^[1] ; Traina, Fablola ^[1] ; da Costa, Fernando Ferreira ^[1] ; de Souza, Carmino Antonio ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, UNICAMP, Hematol & Hemotherapy Ctr, BR-13083878 Campinas, SP - Brazil

^[2] Univ Fed Sao Carlos UFSCAR, Dept Genet & Evolut, Sao Carlos, SP - Brazil

^[3] Univ Estadual Campinas, UNICAMP, Inst Biol, Dept Genet & Evolut, BR-13083878 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Leukemia & Lymphoma; v. 55, n. 8, p. 1861-1869, AUG 2014.
• Citações Web of Science: 4

Resumo

Differential gene expression analysis by suppression subtractive hybridization with correlation to the metabolic pathways involved in chronic myeloid leukemia (CML) may provide a new insight into the pathogenesis of CML. Among the overexpressed genes found in CML at diagnosis are SEPT5, RUNX1, MIER1, KPNA6 and FLT3, while PAN3, TOB1 and ITCH were decreased when compared to healthy volunteers. Some genes were identified and involved in CML for the first time, including TOB1, which showed a low expression in patients with CML during tyrosine kinase inhibitor treatment with no complete cytogenetic response. In agreement, reduced expression of TOB1 was also observed in resistant patients with CML compared to responsive patients. This might be related to the deregulation of apoptosis and the signaling pathway leading to resistance. Most of the identified genes were related to the regulation of nuclear factor kappa B (NF-kappa B), AKT, interferon and interleukin-4 (IL-4) in healthy cells. The results of this study combined with literature data show specific gene pathways that might be explored as markers to assess the evolution and prognosis of CML as well as identify new therapeutic targets. (AU)

• Processo FAPESP: 09/53388-0 - Analise funcional dos genes sept5, tob1 e pan3 em cultura de linhagens celulares baf3, baf3t315l e linhagem granulocitica de pacientes portadores de leucemia mieloide cronica.
• Beneficiário: Cintia Do Couto Mascarenhas
• Modalidade de apoio: Bolsas no Brasil - Doutorado