Lung resistance-related protein (LRP) predicts favorable therapeutic outcome in Acute Myeloid Leukemia

Sci Rep. 2019 Jan 23;9(1):378. doi: 10.1038/s41598-018-36780-8.

Abstract

There is conflicting evidence that MDR1, MRP2 and LRP expression is responsible for chemotherapy resistance. We conducted this study to explore their role in AML therapy outcomes. Bone marrow and peripheral blood samples of 90 AML patients, receiving chemotherapy, were analyzed by real time PCR. Gene expression was calculated by the 2-ΔΔCt method. The patients who had a persistent remission were labelled 'Good Responder' (GRes) whereas, those with relapse or drug resistance were labelled 'Poor Responders' (PRes). Higher LRP expression in bone marrow, but not in peripheral blood, was positively associated with persistent remission (p = 0.001), GRes (p = 0.002), 1-year overall as well as disease-free survival (p = 0.02 and p = 0.007, respectively). Marrow and blood MDR1 and MRP2 expression did not differ significantly between the above groups. Logistic regression analysis showed that only a diagnosis of acute promyelocytic leukemia (APL; M3) or high marrow LRP expression significantly predicted a favorable therapeutic outcome. This is the first report showing that high bone marrow LRP expression predicts significant favorable therapeutic outcome. Peripheral blood LRP expression as well as marrow and blood MDR1 and MRP2 expression have no predictive value in AML patients treated with standard dose cytarabine and daunorubicin 3+7 regimen.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / biosynthesis
  • ATP-Binding Cassette Sub-Family B Member 4
  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Bone Marrow / metabolism*
  • Bone Marrow / pathology
  • Cytarabine / administration & dosage
  • Daunorubicin / administration & dosage
  • Drug Resistance, Neoplasm*
  • Female
  • Humans
  • Leukemia, Promyelocytic, Acute* / drug therapy
  • Leukemia, Promyelocytic, Acute* / metabolism
  • Leukemia, Promyelocytic, Acute* / mortality
  • Male
  • Middle Aged
  • Neoplasm Proteins / biosynthesis*
  • Vault Ribonucleoprotein Particles / biosynthesis*

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • Neoplasm Proteins
  • Vault Ribonucleoprotein Particles
  • major vault protein
  • Cytarabine
  • Daunorubicin