title: Protein-coding genes and long noncoding RNAs are differentially expressed in dasatinib-treated chronic myeloid leukemia patients with resistance to imatinib.
abstract: Dasatinib has demonstrated efficacy in patients with chronic-phase chronic myeloid leukemia (CML) who had resistance or intolerance to imatinib. However, some patients also develop resistance or intolerance to dasatinib. To identify potential molecular pathways involved in primary resistance to dasatinib in CML, we analyzed gene expression profiles of mononuclear cells of 7 imatinib-resistant patients, collected before and after 1-year dasatinib treatment. Large-scale gene expression was measured with Agilent microarrays covering protein-coding genes and long (>200 nt) noncoding RNAs (lncRNAs). Sets of genes and lncRNAs significantly differentially expressed (>1.5 fold-change; q value ≤10%) were identified. Ingenuity Pathway Analysis pointed to a number of functions, canonical pathways and gene networks that were significantly enriched with differentially expressed genes. In addition to protein-coding genes, lncRNAs have been recently implicated in pathways leading to tumorigenesis. Our data point to new possible regulatory elements involved in dasatinib resistance in CML.
authors.forename: Rosana A
authors.initials: RA
authors.lastname: Silveira
authors.forename: Angela A
authors.initials: AA
authors.lastname: Fachel
authors.forename: Yuri B
authors.initials: YB
authors.lastname: Moreira
authors.forename: Carmino A
authors.initials: CA
authors.lastname: De Souza
authors.forename: Fernando F
authors.initials: FF
authors.lastname: Costa
authors.forename: Sergio
authors.initials: S
authors.lastname: Verjovski-Almeida
authors.forename: Katia B B
authors.initials: KB
authors.lastname: Pagnano
mesh_terms: D000328:Adult; D000368:Aged; D001549:Benzamides / Q000494:pharmacology*; D000069439:Dasatinib; D019008:Drug Resistance, Neoplasm; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D000068877:Imatinib Mesylate; D015466:Leukemia, Myeloid, Chronic-Phase / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D062085:RNA, Long Noncoding / Q000235:genetics*; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D062085:RNA, Long Noncoding; D013844:Thiazoles; D000068877:Imatinib Mesylate; D000069439:Dasatinib
keywords: Chronic myeloid leukemia; Dasatinib; Imatinib; Long ncRNAs; Resistance