Summary. Biphenotypic acute leukaemia (BAL) patients represented 8% of the 287 de novo consecutive adult acute leukaemias (23 BAL, 230 acute myeloid leukaemia (AML) and 34 acute lymphoblastic leukaemia (ALL)) referred to our department during the last 4-year period. Of these 23 BAL patients, 14 patients showed myeloid morphology and nine cases lymphoid morphology according to FAB criteria. There were no differences between lymphoid and myeloid BAL according to clinical and biological presentation and treatment outcome. We confirm the poor prognosis of BAL when compared to AML or ALL seen during the same period of time, in terms of complete remission (47%, 62% and 82% respectively, BAL v AML, NS and BAL v ALL, P ¼ 0·006) and 4-year overall survival (8·1%, 25·8% and 23·8% respectively, BAL v AML, P ¼ 0·05 and BAL v ALL, P ¼ 0·003). Comparing adult BAL patients with AML patients, we found an increase in poor prognostic factors: CD34 þ phenotype (82% v 60% respectively, P ¼ 0·03), unfavourable karyotype (60% v 20%, P < 0·0001) and Pgp over-expression by RT-PCR (0·705 v 0·107, P < 0·0001) and flow cytometry (0·824 v 0·391, P ¼ 0·0001). MRP and LRP were not found to be poor prognostic factors. Comparing BAL patients with ALL patients, we found also an increase in poor prognostic factors: age (51 v 39, P ¼ 0·003) and CD34 þ phenotype (82% v 50%, P ¼ 0·02). We conclude that BAL patients need a more aggressive treatment procedure, including high-dose AraC or the use of Pgp modulators for first-line therapy.

Purpose: 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.Experimental Design: 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.

Purpose: 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. Experimental Design and 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.