title: P-glycoprotein and multidrug resistance associated protein-1 activity in 132 acute myeloid leukemias according to FAB subtypes and cytogenetics risk groups.
abstract: OBJECTIVE
  We studied the function of both Pgp and MRP1 to identify subgroups of patients who could benefit from Pgp reversion, and to clarify in different FAB subtypes and in cytogenetic risk groups their expression and function.
  
  
  METHODS
  We examined 132 adults with de novo acute myeloid leukemia (AML) for Pgp and MRP1 expression and function. We correlated our finding with the FAB subtypes and the cytogenetics, and clinical data of our patients.
  
  
  RESULTS
  Among FAB subtypes and cytogenetic subgroups, patients with good risk cytogenetics have a low expression and activity of Pgp and MRP1 except patients with inv(16) who have a higher activity of MRP1 than t(8;21) and t(15;17) (p=0.05). All other AML patients, except M5, have a high expression and activity of Pgp. In contrast, M5 have a high expression, but a low activity of Pgp. In this subgroup, M5 with MLL gene rearrangement did not express an active Pgp. Others patients with M5 AML did not have a functional Pgp. Monosomy 7, 11q2.3 gene rearrangement and complex cytogenetic have a higher activity of MRP1 than other cytogenetic (p=0.03).
  
  
  CONCLUSIONS
  Resistance mechanism in M5 was not mediated by Pgp. In contrast, MRP1 may play a role in patients who have a 11q2.3 gene rearrangement, or in M4E with inv(16). Thus trials that modulate Pgp are likely to achieve limited success in AML with low activity of Pgp, i.e., M5 and, AML with good risk cytogenetics.
authors.affiliation: Laboratoire E 03-55 INSERM, EA 1529, Université Paris VI, France. ollivier.legrand@htd.ap-hop-paris.fr
authors.forename: Ollivier
authors.initials: O
authors.lastname: Legrand
authors.forename: Simona
authors.initials: S
authors.lastname: Zompi
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Perrot
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Faussat
authors.forename: Zineb
authors.initials: Z
authors.lastname: Benderra
authors.forename: Driss
authors.initials: D
authors.lastname: Chaoui
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Marie
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000378:metabolism*; D000208:Acute Disease; D000328:Adult; D007446:Chromosome Inversion / Q000235:genetics; D003582:Cytogenetics / Q000379:methods*; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics / Q000473:pathology; D007947:Leukemia, Megakaryoblastic, Acute / Q000235:genetics / Q000473:pathology; D007948:Leukemia, Monocytic, Acute / Q000235:genetics / Q000473:pathology; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000473:pathology*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000473:pathology; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics / Q000473:pathology; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000473:pathology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D009363:Neoplasm Proteins / Q000096:biosynthesis; D011379:Prognosis; D012307:Risk Factors; D014178:Translocation, Genetic / Q000235:genetics; D020394:Vault Ribonucleoprotein Particles / Q000096:biosynthesis; D000099187:Major Vault Protein
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; C421109:multidrug resistance-associated protein 1