title: Apoptosis-related gene expression profile in chronic myeloid leukemia patients after imatinib mesylate and dasatinib therapy.
abstract: OBJECTIVE
  We investigated the effects of tyrosine kinase inhibitors (TKIs) on the expression of apoptosis-related genes (BCL-2 and death receptor family members) in chronic myeloid leukemia (CML) patients.
  
  
  METHODS
  Peripheral blood mononuclear cells from 32 healthy subjects and 26 CML patients were evaluated before and after treatment with imatinib mesylate (IM) and dasatinib (DAS) by quantitative PCR.
  
  
  RESULTS
  Anti-apoptotic genes (c-FLIP and MCL-1) were overexpressed and the pro-apoptotic BIK was reduced in CML patients. Expression of BMF, A1, c-FLIP, MCL-1, CIAP-2 and CIAP-1 was modulated by DAS. In IM-resistant patients, expression of A1, c-FLIP, CIAP-1 and MCL-1 was upregulated, and BCL-2, CIAP-2, BAK, BAX, BIK and FASL expression was downregulated.
  
  
  CONCLUSIONS
  Taken together, our results point out that, in CML, DAS interferes with the apoptotic machinery regulation. In addition, the data suggest that apoptosis-related gene expression profiles are associated with primary resistance to IM.
authors.forename: Aline Fernanda
authors.initials: AF
authors.lastname: Ferreira
authors.forename: Gislane L V
authors.initials: GLV
authors.lastname: de Oliveira
authors.forename: Raquel
authors.initials: R
authors.lastname: Tognon
authors.forename: Maria Dulce S
authors.initials: MDS
authors.lastname: Collassanti
authors.forename: Maria Aparecida
authors.initials: MA
authors.lastname: Zanichelli
authors.forename: Nelson
authors.initials: N
authors.lastname: Hamerschlak
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: de Souza
authors.forename: Dimas Tadeu
authors.initials: DT
authors.lastname: Covas
authors.forename: Simone
authors.initials: S
authors.lastname: Kashima
authors.forename: Fabiola Attie
authors.initials: FA
authors.lastname: de Castro
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001549:Benzamides / Q000494:pharmacology* / Q000627:therapeutic use*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000235:genetics / Q000378:metabolism; D000069439:Dasatinib; D019008:Drug Resistance, Neoplasm; D004359:Drug Therapy, Combination; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology* / Q000627:therapeutic use*; D059467:Transcriptome
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D001549:Benzamides; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D012333:RNA, Messenger; D013844:Thiazoles; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; D000069439:Dasatinib