title: Do SLCO1B3 (T334G) and CYP3A5*3 polymorphisms affect response in Egyptian chronic myeloid leukemia patients receiving imatinib therapy?
abstract: BACKGROUND
  Imatinib has so far been the first-choice treatment in chronic myeloid leukemia (CML) with excellent results. However, only a proportion of patients achieve major molecular response. Hence, the need to find whether there are some factors that affect the response to treatment is essential. This study aimed to investigate the allele and genotype frequencies of single nucleotide polymorphisms (SNPs) of SLCO1B3 (T334G) and CYP3A5*3 in CML patients undergoing imatinib treatment and to determine whether SNPs of these two genes could predict the response of imatinib therapy in CML patients.
  
  
  METHODS
  We investigated SLCO1B3 (T334G) and CYP3A5*3 polymorphisms by Polymerase Chain Reaction-restriction fragment length polymorphism in 86 Philadelphia positive newly diagnosed Egyptian CML patients (78 patients in chronic phase and 8 patients in accelerated phase). All patients received imatinib therapy and were followed for at least one and half years. The response to imatinib therapy was evaluated by recording the hematological response, cytogenetic response, and molecular response according to the European Leukemia Net criteria.
  
  
  RESULTS
  This study included 86 Philadelphia positive newly diagnosed CML patients, 78 in the early chronic phase and 8 in the accelerated phase. In the chronic phase patients, no association between SLCO1B3 (T334G) exon 3 polymorphism and response to imatinib therapy was detected (P = 0.938) while CYP3A5*3 gene polymorphism was associated with inferior outcome (P < 0.001). In the group of accelerated phase patients, the SLCO1B3 polymorphic variants (TG) and (GG) were detected equally with none of the patients in this group having the homozygous wild form (TT). The homozygous state for the CYP3A5*3 allele was the most frequent (50%) and the homozygous state for the CYP3A5*1 allele was the least frequent (12.5%) in this group.
  
  
  CONCLUSIONS
  CYP3A5*3 polymorphism was associated with imatinib efficacy while the SNP SLCO1B3 (T334G) was not associated with the response to imatinib treatment in Egyptian patients with CML in chronic phase. These results prompt us to explore the effect of CYP3A5*3 in CML patients taking imatinib in a larger scale study.
authors: Department of Hematology, Medical Research Institute, Alexandria University, Alexandria, Egypt. dr_ahmed_bedewy@yahoo.com
authors: Ahmed M L
authors: AM
authors: Bedewy
authors: Shereen M
authors: SM
authors: El-Maghraby
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides / Q000627:therapeutic use*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000378:metabolism; D004534:Egypt; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics*; D010879:Piperazines / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011743:Pyrimidines / Q000627:therapeutic use*; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D029362:Organic Anion Transporters, Sodium-Independent; D010879:Piperazines; D011743:Pyrimidines; C421209:SLCO1B3 protein, human; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D000068877:Imatinib Mesylate; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A