title: XPD gene polymorphisms and the effects of induction chemotherapy in cytogenetically normal de novo acute myeloid leukemia patients.
abstract: BACKGROUND
  Cytogenetically normal acute myeloid leukemia (AML) represents nearly half of newly diagnosed de novo AML cases. XPD is one of the DNA repair proteins, whose genetic polymorphisms are thought to affect their function as regards response to chemotherapeutic drugs and chemotherapy-induced toxicities.
  
  
  METHODS
  We investigated the XPD Asp312Asn and Lys751Gln polymorphisms by polymerase chain reaction-restriction fragment length polymorphism in 51 newly diagnosed cytogenetically normal de novo AML patients. The response to the standard induction chemotherapy protocol and chemotherapy-induced toxicities were monitored.
  
  
  RESULTS
  The XPD Asp312Asn GG genotype was the most frequent (57%) followed by the GA variant (37%), and the AA variant was the least frequent (6%). As regards the XPD Lys751Gln polymorphism, the AA genotype was the most frequent (49%), followed by the AC (39%) and CC (12%) variants. These variants were not associated with age, sex, FAB subtype, CNS infiltration, chemotherapy-induced hepatotoxicity, nephrotoxicity, or metabolic toxicity. The XPD Lys751Gln CC polymorphic variant was associated with chemotherapy-induced cardiotoxicity and lower chance to achieve response to induction chemotherapy.
  
  
  CONCLUSIONS
  XPD Lys751Gln and not Asp312Asn polymorphism was associated with chemotherapy-induced cardiotoxicity and response to induction chemotherapy in newly diagnosed cytogenetically normal AML patients. Pretreatment assay of XPD Lys751Gln may help to anticipate cardiotoxicity in those at risk. Moreover, it may be considered a prognostic marker in AML cases. However, further large scale research is needed to verify its usefulness.
authors.forename: Mervat A
authors.initials: MA
authors.lastname: El-Tokhy
authors.forename: Neveen A
authors.initials: NA
authors.lastname: Hussein
authors.forename: Ahmed M L
authors.initials: AM
authors.lastname: Bedewy
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Barakat
mesh_terms: D000208:Acute Disease; D000328:Adult; D019943:Amino Acid Substitution; D016009:Chi-Square Distribution; D020732:Cytogenetic Analysis; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006331:Heart Diseases / Q000139:chemically induced; D006801:Humans; D060828:Induction Chemotherapy / Q000009:adverse effects; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009010:Monte Carlo Method; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D012307:Risk Factors; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*; D055815:Young Adult
chemical_list: D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human
keywords: AML; Chemotherapy; XPD