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

Bibi Kulsoom,Nasir Ali Afsar,Tahir Sultan Shamsi

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.

Highlights

One of the ABC transporter family member, ABCB1, called multidrug resistance protein 1 (MDR1) or permeability-glycoprotein (P-gp), is involved in cellular efflux of xenobiotics, including chemotherapeutic agents
Medians and interquartile ranges (IQRs) for MDR1, multidrug resistance-associated protein 2 (MRP2) and lung resistance-related protein (LRP) gene expression are given in Table 2, and boxplots using a logarithmic scale are given in Supplementary Fig. 1
Median bone marrow LRP expression was higher in subgroups with a better clinical outcome, i.e. acute promyelocytic leukemia (APL), negative MPO, persistent remission and being alive

Summary

Introduction

One of the ABC transporter family member, ABCB1, called multidrug resistance protein 1 (MDR1) or permeability-glycoprotein (P-gp), is involved in cellular efflux of xenobiotics, including chemotherapeutic agents. Researchers have focused on MDR1 expression in many drug resistant hematological and solid cancers, yielding inconsistent results[5,6,7,8,9,10]. Another ABC transporter, ABCC2, called multidrug resistance-associated protein 2 (MRP2), (formerly known as canalicular multispecific organic anion transporter - cMOAT) is commonly found on hepatocyte canaliculi, intestines and kidney cells, and transports various chemicals including drugs[11]. MPO status FLT3 mutation NPM1 mutation PML-RAR mutation MLL mutation Karyotyping Therapeutic response Survival status Final outcome

Methods

Results

Conclusion