BCRP mRNA and FLT3-ITD are independent poor risk factors in adult patients with acute myeloid leukemia and intermediate or normal karyotype

Eur J Haematol. 2017 Sep;99(3):255-261. doi: 10.1111/ejh.12913. Epub 2017 Jul 17.

Abstract

Purpose: FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) is aberration associated with poor prognosis in AML. We have analyzed the expression of MDR-1, MRP-1, and BCRP mRNA in relation to FLT3-ITD in 100 AML adult patients with normal and intermediate karyotype.

Methods: The RQ-PCR method was performed to assess the expression of MDR-1, MRP-1, and BCRP mRNA, and the results were presented as coefficients calculated using an intermediate method according to Pfaffl's rule.

Results: According to univariate analysis, the following pretreatment variables negatively influenced disease-free survival (DFS): WBC count ≥25×109 /L (P=.037), MRP-1 mRNA ≥1.6818 (P=.028), BCRP mRNA ≥1.1892 (P=.004), FLT3-ITD (P=.005) and overall survival (OS): WBC count ≥25×109 /L (P=.031), MRP-1 mRNA ≥1.6818 (P=.01), BCRP mRNA ≥1.1892 (P=.01), FLT3-ITD (P=.001). When all prognostic variables were pooled into a multivariate model, we found that WBC count ≥25×109 /L (P=.026) and BCRP mRNA ≥1.1892 (P=.011). We observed trend in negative influence of FLT3-ITD on DFS (P=.057). BCRP mRNA ≥1.1892 (P=.035) and FLT3-ITD (P=.006) negatively, independently influenced the OS.

Conclusions: The high expressions of BCRP mRNA calculated with Pfaffl's rule and FLT3-ITD are independent poor risk factors in adult patients with AML and intermediate or normal karyotype.

Keywords: BCRP mRNA; FLT3-ITD; acute myeloid leukemia.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / genetics*
  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor
  • Female
  • Gene Duplication*
  • Gene Expression
  • Humans
  • Karyotype*
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / mortality*
  • Leukemia, Myeloid, Acute / therapy
  • Male
  • Middle Aged
  • Mutation Rate
  • Neoplasm Proteins / genetics*
  • Prognosis
  • RNA, Messenger / genetics*
  • Survival Analysis
  • Tandem Repeat Sequences*
  • Young Adult
  • fms-Like Tyrosine Kinase 3 / genetics*

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • Biomarkers, Tumor
  • Neoplasm Proteins
  • RNA, Messenger
  • fms-Like Tyrosine Kinase 3