Beclin-1 and hypoxia-inducible factor-1α genes expression: Potential biomarkers in acute leukemia patients

Cancer Biomark. 2016 Mar 18;16(4):619-26. doi: 10.3233/CBM-160603.

Abstract

Background: Beclin-1, an important autophagic gene, and hypoxia-inducible factor-1α (HIF-1α), the master regulator of the hypoxic response, are reported in several human cancers. However, their expressions in acute leukemia haven't yet been well investigated.

Objective: This study was designed to investigate the gene expression of beclin-1, microtubule-associated protein-1 light chain-3B (MAB1LC3B), the anti-apoptotic marker Bcl-2, and HIF-1α, as well as to evaluate the relationship between their expressions profile and prognosis in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) adult patients.

Methods: The study involved 30 AML patients, 25 ALL patients, and 20 controls. Gene expression was analyzed using quantitative reverse transcriptase polymerase chain reaction (QRT-PCR).

Results: In both AML and ALL groups, beclin-1 and MAB1LC3B expressions were significantly down-regulated (p < 0.001), while HIF-1α (p < 0.01) and Bcl-2 (p < 0.001) expressions were significantly up-regulated compared to the control group. HIF-1α fold expression was significantly negatively correlated with beclin-1 (p < 0.01). Moreover, decreased beclin-1 gene expression and increased HIF-1α gene expression were both associated with poor survival, supporting their pivotal role in the development and progression of acute leukemia.

Conclusions: Both Beclin-1 and HIF-1α could be considered as important biomarkers determinants of pathogenesis and survival in acute leukemia.

Keywords: Acute leukemia; Beclin-1; HIF-1α; MAP1LC3B; autophagy.

MeSH terms

  • Beclin-1 / genetics*
  • Beclin-1 / metabolism
  • Biomarkers
  • Female
  • Gene Expression Regulation, Leukemic*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Immunophenotyping
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / therapy
  • Male
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism

Substances

  • Beclin-1
  • Biomarkers
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Proto-Oncogene Proteins c-bcl-2