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Tsuji K, Wang YH, Takanashi M, et al. Overexpression of lung resistance-related protein and P-glycoprotein and response to induction chemotherapy in acute myelogenous leukemia. Hematol Rep. 2012;4(3):e18doi: 10.4081/hr.2012.e18.
Tsuji, K., Wang, Y. H., Takanashi, M., Odajima, T., Lee, G. A., Sugimori, H., & Motoji, T. (2012). Overexpression of lung resistance-related protein and P-glycoprotein and response to induction chemotherapy in acute myelogenous leukemia. Hematology reports, 4(3), e18. https://doi.org/10.4081/hr.2012.e18
Tsuji, Kazue, et al. "Overexpression of lung resistance-related protein and P-glycoprotein and response to induction chemotherapy in acute myelogenous leukemia." Hematology reports vol. 4,3 (2012): e18. doi: https://doi.org/10.4081/hr.2012.e18
Tsuji K, Wang YH, Takanashi M, Odajima T, Lee GA, Sugimori H, Motoji T. Overexpression of lung resistance-related protein and P-glycoprotein and response to induction chemotherapy in acute myelogenous leukemia. Hematol Rep. 2012 Jul 11;4(3):e18. doi: 10.4081/hr.2012.e18. Epub 2012 Oct 01. PMID: 23087807; PMCID: PMC3475940.
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Hematol Rep. 2012 Jul 11;4(3):e18. doi: 10.4081/hr.2012.e18. Epub 2012 Oct 01.

Overexpression of lung resistance-related protein and P-glycoprotein and response to induction chemotherapy in acute myelogenous leukemia.

Hematology reports

Kazue Tsuji, Yan-Hua Wang, Minoko Takanashi, Tsuyoshi Odajima, Gabriel A Lee, Hiroki Sugimori, Toshiko Motoji

Affiliations

  1. Department of Hematology, Tokyo Women's Medical University;

PMID: 23087807 PMCID: PMC3475940 DOI: 10.4081/hr.2012.e18

Abstract

Lung resistance-related protein (LRP) and P-glycoprotein (P-gp) are associated with multidrug resistance. P-gp overexpression reduces intracellular anticancer drug concentrations and is correlated with low remission rates. However, whether the presence of LRP influences the response to induction chemotherapy remains controversial. Therefore, we investigated the relationship of LRP and P-gp overexpression with the response to induction chemotherapy. Univariate analysis revealed that there was a significant difference between complete remission rates for acute myelogenous leukemia patients depending on their blast cell expressions, between LRP positive versus negative, P-gp positive versus negative, and LRP/P-gp double positive versus other groups. Crude odds ratios (ORs) for complete remission were 0.390, 0.360, and 0.307 for LRP positive, for P-gp positive, and LRP/P-gp double positive patients, respectively. After controlling the confounding variables by stepwise multivariate logistical regression analysis, the presence of LRP/P-gp double positivity and P-gp positivity were found to be independent prognostic factors; adjusted ORs were 0.233 and 0.393, respectively. Furthermore, the monoclonal antibody against LRP significantly increased daunorubicin acumulation (P=0.004) in the nuclei of leukemic blast cells with LRP positivity in more than 10% of the cells. An LRP reversing agent, PAK-104P, was found to increase the daunorubicin content with marginal significance (P=0.060). The present results suggest that not only the presence of P-gp, but also LRP in leukemic blast cells is a risk factor for resistance to induction chemotherapy. Inhibiting LRP function, similar to the inhibition of P-gp function, will be necessary to improve the effectiveness of induction chemotherapy.

Keywords: P-glycoprotein; acute myelogenous leukemia.; lung resistance-related protein; reversing agent

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