title: Association between P-glycoprotein and lymphoid antigen expression on myeloblasts versus therapy response and survival in de novo acute myeloid leukemia: long-term follow-up results.
abstract: P-glycoprotein (PGP) over-expression on malignant cells is associated with poor prognosis and treatment outcome due to the development of a multidrug resistance phenotype. In this study, we analyzed the correlation between expression of PGP and lymphoid antigens (Ly) on leukemic myeloblasts versus response to therapy and survival in acute myeloid leukemia (AML). Fifty-one consecutive patients, aged 16-75 (median age 44.6 years), diagnosed with de novo AML between 1997 and 2000, and who received at least one induction chemotherapy course, were enrolled in the study. Expression of PGP on ≥ 10% of the myeloblasts (PGP(+)AML) at the time of diagnosis was observed in 21 patients (41%). The complete remission rate did not differ between PGP(+) (13/21) and PGP(-) (20/30) patients (62 vs. 67%). Twelve of the 51 patients (24%) were still alive after a median follow-up time of 11.5 years (range 10.7-13.1). The Ly(+)AML patients showed significantly better overall survival compared with Ly(-)AML patients (8/18 vs. 4/33 patients alive at the last follow-up, P = 0.003). The subgroup of patients with co-expression of PGP and Ly also showed better overall survival compared with PGP(+)AML patients without Ly expression (4/8 vs. 0/13 patients alive at the last follow-up; P = 0.04). Our results suggest that expression of lymphoid antigens on PGP(+) myeloblasts in AML can positively affect survival in AML patients, mainly due to a decreased relapse risk and better survival. Although the small number of patient may be perceived as a limitation of the study, the long follow-up period strengthens its value. Further prospective trials are needed to obtain more information concerning the association between PGP and lymphoid antigens in AML, which would put our results in their ultimate proper context.
authors.affiliation: Division of Hematology, Department of Medicine at Huddinge, Karolinska Institutet, and Hematology Center Karolinska, M54, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden. maciej.machaczka@ki.se
authors.forename: Maciej
authors.initials: M
authors.lastname: Machaczka
authors.forename: Björn Engelbrekt
authors.initials: BE
authors.lastname: Wahlin
authors.forename: Beata
authors.initials: B
authors.lastname: Piatkowska-Jakubas
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Rucinska
authors.forename: Wojciech
authors.initials: W
authors.lastname: Jurczak
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Balana-Nowak
authors.forename: Monika
authors.initials: M
authors.lastname: Klimkowska
authors.forename: Hans
authors.initials: H
authors.lastname: Hägglund
authors.forename: Aleksander B
authors.initials: AB
authors.lastname: Skotnicki
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis / Q000096:biosynthesis*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000950:Antigens, Ly; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D005434:Flow Cytometry; D042381:Granulocyte Precursor Cells / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D055815:Young Adult
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000950:Antigens, Ly; D014408:Biomarkers, Tumor