Breast cancer resistance protein and P-glycoprotein in 149 adult acute myeloid leukemias.
OBJECTIVE
Recently, a new ABC protein, breast cancer resistance protein (BCRP), was described. But its prognosis is not known in acute myeloid leukemia (AML). In addition, the prognosis of P-glycoprotein (Pgp) and BCRP in patients treated homogeneously by the same anthracycline (daunorubicin, idarubicin, or mitoxantrone) during all of the treatment with aracytine is not known. Therefore, we have evaluated the relationship between drug resistance phenotype, in vitro anthracene sensitivity, and the relation to treatment outcome.


METHODS
We have analyzed 149 AML treated according to protocol of the European Organization for Research and Treatment of Cancer group. The prognostic value of BCRP and Pgp were analyzed in the whole population and according to intercalating agent.


RESULTS
BCRP was a prognostic factor, for achievement of complete remission (43% in positive patients and 69% in negative patients, P = 0.005), the 4-year disease-free survival (12% versus 33%, P = 0.03), and the 4-year overall survival (19% versus 38%, P = 0.003). When BCRP expression and Pgp function were categorized in three groups, +/+, +/- or -/+, and -/-, the achievement of complete remission was 45%, 66%, and 90% (P = 0.0003), the 4-year disease-free survival was 8%, 26%, and 40% (P = 0.01), and the 4-year overall survival was 16%, 37%, and 48% (P = 0.001), respectively. Pgp function was a prognostic factor in patients treated by daunorubicin and idarubicin but not by mitoxantrone. In contrast, BCRP expression was a prognostic factor in patients treated by daunorubicin and mitoxantrone but not by idarubicin.


CONCLUSIONS
BCRP would be implicated in the resistance to chemotherapies in AML. But these are the patients expressing both BCRP and Pgp who have the poorest prognosis.
Benderra
Zineb
Z
Département d'Hématologie Clinique, Laboratoire INSERM, Universitaire Paris 6, Hôpital Hôtel-Dieu, Paris, France.
Faussat
Anne-Marie
AM
Sayada
Lydia
L
Perrot
Jean-Yves
JY
Chaoui
Driss
D
Marie
Jean-Pierre
JP
Legrand
Ollivier
O
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000208:Acute Disease; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D018572:Disease-Free Survival; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000188:drug therapy; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
C116614:ABCG2 protein, human; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D003561:Cytarabine; D008942:Mitoxantrone; D015255:Idarubicin; D003630:Daunorubicin