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The prognostic significance of the expression and function of multidrug resistance transporter proteins in acute myeloid leukemia: studies of the Southwest Oncology Group Leukemia Research Program.
Semin Hematol. 1997 Oct; 34(4 Suppl 5):25-33.SH

Abstract

Resistance to chemotherapy is a major obstacle in the treatment of patients with acute myeloid leukemia (AML). The majority of AML patients are intrinsically resistant to chemotherapy at initial diagnosis before chemotherapeutic exposure; such intrinsic resistance frequently results from expression of the multidrug resistance gene (MDR-1), which encodes a membrane transporter protein, P-glycoprotein (P-gp), that mediates drug efflux in leukemic cells. Expression of novel transporter proteins that confer alternative forms of multidrug resistance (MDR), such as the lung-resistance protein (LRP) and the MDR-associated protein (MRP), occurs more frequently in leukemic patients at relapse. Preliminary studies indicate that these proteins may also confer therapeutic resistance in leukemia. In patients older than 55 years of age, AML is characterized by a high frequency of unfavorable cytogenetics, P-gp expression, and functional drug efflux, which contribute to poor clinical outcome. In a multivariate analysis, secondary AML, unfavorable cytogenetics, and P-gp expression/function were each significantly and independently associated with a lower complete remission (CR) rate. Resistant disease was associated with P-gp expression and unfavorable cytogenetics. Strikingly, elderly patients with P-gp- de novo AML and favorable or intermediate cytogenetics had a CR rate of 81%. Patients with P-gp+ secondary AML with unfavorable cytogenetics had a CR rate of only 12%. Therefore, characterization of elderly AML patients at diagnosis using biologic parameters may help identify those patients who are likely to achieve a CR with conventional regimens, as well as those patients who require alternate treatment designed to overcome MDR. In contrast, expression of P-gp and functional drug efflux is detected in only 25% to 30% of AML patients less than 50 years of age. While P-gp expression is less strongly associated with a poor outcome in younger versus older AML patients, it remains strongly associated with resistant disease. Studies are ongoing to determine the prognostic significance of LRP and MRP in various forms of leukemia.

Authors+Show Affiliations

UNM Center for Molecular and Cellular Diagnostics, University of New Mexico Cancer Center, Albuquerque 87131, USA. cwillman@cobra.unm.edu

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9408958

Citation

Willman, C L.. "The Prognostic Significance of the Expression and Function of Multidrug Resistance Transporter Proteins in Acute Myeloid Leukemia: Studies of the Southwest Oncology Group Leukemia Research Program." Seminars in Hematology, vol. 34, no. 4 Suppl 5, 1997, pp. 25-33.
Willman CL. The prognostic significance of the expression and function of multidrug resistance transporter proteins in acute myeloid leukemia: studies of the Southwest Oncology Group Leukemia Research Program. Semin Hematol. 1997;34(4 Suppl 5):25-33.
Willman, C. L. (1997). The prognostic significance of the expression and function of multidrug resistance transporter proteins in acute myeloid leukemia: studies of the Southwest Oncology Group Leukemia Research Program. Seminars in Hematology, 34(4 Suppl 5), 25-33.
Willman CL. The Prognostic Significance of the Expression and Function of Multidrug Resistance Transporter Proteins in Acute Myeloid Leukemia: Studies of the Southwest Oncology Group Leukemia Research Program. Semin Hematol. 1997;34(4 Suppl 5):25-33. PubMed PMID: 9408958.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The prognostic significance of the expression and function of multidrug resistance transporter proteins in acute myeloid leukemia: studies of the Southwest Oncology Group Leukemia Research Program. A1 - Willman,C L, PY - 1997/12/31/pubmed PY - 1997/12/31/medline PY - 1997/12/31/entrez SP - 25 EP - 33 JF - Seminars in hematology JO - Semin Hematol VL - 34 IS - 4 Suppl 5 N2 - Resistance to chemotherapy is a major obstacle in the treatment of patients with acute myeloid leukemia (AML). The majority of AML patients are intrinsically resistant to chemotherapy at initial diagnosis before chemotherapeutic exposure; such intrinsic resistance frequently results from expression of the multidrug resistance gene (MDR-1), which encodes a membrane transporter protein, P-glycoprotein (P-gp), that mediates drug efflux in leukemic cells. Expression of novel transporter proteins that confer alternative forms of multidrug resistance (MDR), such as the lung-resistance protein (LRP) and the MDR-associated protein (MRP), occurs more frequently in leukemic patients at relapse. Preliminary studies indicate that these proteins may also confer therapeutic resistance in leukemia. In patients older than 55 years of age, AML is characterized by a high frequency of unfavorable cytogenetics, P-gp expression, and functional drug efflux, which contribute to poor clinical outcome. In a multivariate analysis, secondary AML, unfavorable cytogenetics, and P-gp expression/function were each significantly and independently associated with a lower complete remission (CR) rate. Resistant disease was associated with P-gp expression and unfavorable cytogenetics. Strikingly, elderly patients with P-gp- de novo AML and favorable or intermediate cytogenetics had a CR rate of 81%. Patients with P-gp+ secondary AML with unfavorable cytogenetics had a CR rate of only 12%. Therefore, characterization of elderly AML patients at diagnosis using biologic parameters may help identify those patients who are likely to achieve a CR with conventional regimens, as well as those patients who require alternate treatment designed to overcome MDR. In contrast, expression of P-gp and functional drug efflux is detected in only 25% to 30% of AML patients less than 50 years of age. While P-gp expression is less strongly associated with a poor outcome in younger versus older AML patients, it remains strongly associated with resistant disease. Studies are ongoing to determine the prognostic significance of LRP and MRP in various forms of leukemia. SN - 0037-1963 UR - https://www.unboundmedicine.com/medline/citation/9408958/The_prognostic_significance_of_the_expression_and_function_of_multidrug_resistance_transporter_proteins_in_acute_myeloid_leukemia:_studies_of_the_Southwest_Oncology_Group_Leukemia_Research_Program_ DB - PRIME DP - Unbound Medicine ER -