P-glycoprotein and multidrug resistance-associated protein-1 expression in acute myeloid leukemia: Biological and prognosis implications

Int J Lab Hematol. 2020 Oct;42(5):594-603. doi: 10.1111/ijlh.13241. Epub 2020 May 26.

Abstract

Background: Despite the advances in the cure rate for acute myeloid leukemia (AML), a considerable number of patients die from the disease due to the occurrence of multidrug resistance (MDR). Overexpression of the transporter proteins, such as P-glycoprotein (Pgp) and multidrug resistance-associated protein (MRP), confers resistance to the treatment of these leukemias.

Methods: To analyze the expression of the Pgp and MRP1 in patients with AML and determine their correlation between expression and demographic, clinical, and laboratorial variables, bone marrow and peripheral blood samples from 346 patients with a diagnosis of AML were assessed for the expression of Pgp and MRP1 by flow cytometry.

Results: The expression of Pgp and MRP1 was found in 111 (32.1%) and 133 (38.4%) patients, respectively, with greater prevalence in older patients and lower in children, while also observing a high incidence in patients with refractory, recurrence, and secondary disease in comparison with the cases of de novo AML. Regarding the laboratory findings, we observed an association between the expression of Pgp and MRP1 and CD34, CD7, and also M7, M5a, and M2-AML of French-American-British classification.

Conclusions: The results showed that the detection of MDR phenotype by flow cytometry can be a molecular marker for prognosis of patients with AML.

Keywords: P-glycoprotein; acute myeloid leukemia; multidrug resistance; multidrug resistance-associated protein1.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Biomarkers, Tumor
  • Child
  • Child, Preschool
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Female
  • Flow Cytometry
  • Humans
  • Immunophenotyping
  • Infant
  • Leukemia, Myeloid, Acute / diagnosis*
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / mortality
  • Male
  • Middle Aged
  • Multidrug Resistance-Associated Proteins / genetics*
  • Multidrug Resistance-Associated Proteins / metabolism
  • Phenotype
  • Prognosis
  • Symptom Assessment
  • Young Adult

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Biomarkers
  • Biomarkers, Tumor
  • Multidrug Resistance-Associated Proteins
  • multidrug resistance-associated protein 1