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

• Published in: Leukemia & lymphoma 2014-08, Vol.55 (8), p.1861-1869
• Main Authors: Mascarenhas, Cintia do Couto, Ferreira da Cunha, Anderson, Brugnerotto, Ana Flávia, Gambero, Sheley, de Almeida, Maria Helena, Carazzolle, Marcelo F., Pagnano, Katia Borgia Barbosa, Traina, Fabíola, Costa, Fernando Ferreira da, de Souza, Carmino Antonio
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Case-Control Studies; Chronic myeloid leukemia; Female; Gene Expression Profiling; Gene Expression Regulation, Leukemic - drug effects; Gene Regulatory Networks; Granulocytes - drug effects; Granulocytes - metabolism; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - metabolism; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Male; Middle Aged; Molecular Sequence Annotation; Neoplasm Staging; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Signal Transduction; suppression subtractive hybridization; Transcriptome; Treatment Outcome; tyrosine kinase inhibitors; Young Adult
• ISSN: 1042-8194; 1029-2403
• DOI: 10.3109/10428194.2013.855311

Abstract 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 κB (NF-κB), 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.