P-glycoprotein and multidrug resistance associated protein-1 activity in 132 acute myeloid leukemias according to FAB subtypes and cytogenetics risk groups.
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.
Legrand
Ollivier
O
Laboratoire E 03-55 INSERM, EA 1529, Université Paris VI, France. ollivier.legrand@htd.ap-hop-paris.fr
Zompi
Simona
S
Perrot
Jean-Yves
JY
Faussat
Anne-Marie
AM
Benderra
Zineb
Z
Chaoui
Driss
D
Marie
Jean-Pierre
JP
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
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