MRP3, BCRP, and P-glycoprotein activities are prognostic factors in adult acute myeloid leukemia.
OBJECTIVE
P-Glycoprotein (Pgp) is associated with poor outcome in acute myeloid leukemia (AML). We have investigated other ATP-binding cassette proteins such as BCRP, MRP1, MRP2, MRP3, and MRP5 for their potential implication in chemoresistance.


RESULTS
Eighty five AML patient samples were analyzed in this study. First, MRP3 function was higher in patients which had a high level of leukocytes (P = 0.01), a M5 FAB subtype (P = 0.04), and an intermediate or poor cytogenesis (P = 0.05). BCRP activity was not correlated with clinical or biological variables, but high Pgp activity was correlated with the following variables: CD34 expression (P = 0.002), FAB subtype (P = 0.002), intermediate or poor cytogenesis (P = 0.02), and elderly patients (P = 0.03). Second, Pgp, MRP3, and BCRP activities were correlated with complete remission (P = 0.02, P = 0.04, and P = 0.04, respectively), disease-free survival (P = 0.02, P = 0.03, and P = 0.25, respectively), and overall survival (P = 0.04, P = 0.04, and P = 0.05, respectively) in multivariate analysis. The patient samples expressing one or none of these Pgp, MRP3, or BCRP functional proteins have a better prognosis than the patients expressing two or three of these functional proteins (complete remission, P = 0.02; disease-free survival, P = 0.01; overall survival, P < 0.001).


CONCLUSIONS
BCRP and MRP3 may also be involved in chemoresistance in AML, especially MRP3 in patients with M5 FAB. Additional modulation of BCRP or MRP3 to Pgp modulation may be necessary in some patients in order to improve the treatment outcome.
Benderra
Zineb
Z
Laboratoire Institut National de la Sante et de la Recherche Medicale (INSERM U736), Universitaire Paris 6 (UMR 736), France.
Faussat
Anne Marie
AM
Sayada
Lydia
L
Perrot
Jean-Yves
JY
Tang
Ruoping
R
Chaoui
Driss
D
Morjani
Hamid
H
Marzac
Christophe
C
Marie
Jean-Pierre
JP
Legrand
Ollivier
O
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000502:physiology*; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000096:biosynthesis; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020014:K562 Cells; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D015233:Models, Statistical; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis / Q000502:physiology*; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000502:physiology*; D011379:Prognosis; D013997:Time Factors; D016896:Treatment Outcome
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D018952:Antigens, CD34; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; C116614:ABCG2 protein, human; C114462:multidrug resistance-associated protein 3