Overexpression of BAMBI and SMAD7 impacts prognosis of acute myeloid leukemia patients: A potential TERT non-canonical role

Cancer Biomark. 2021;31(1):47-58. doi: 10.3233/CBM-200927.

Abstract

Background: Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) and mothers against decapentaplegic homolog 7 (SMAD7) are important transforming growth factor-β (TGF-β) signaling antagonists, however their roles in acute myeloid leukemia (AML) remains unclear. Telomerase reverse transcriptase (TERT) may be involved in regulating BAMBI and SMAD7 expressions; a role beyond telomeres that is not clinically validated yet.

Objective: In this study, we examined the expression levels and prognostic values of BAMBI, SMAD7 and TERT and their association with AML patients' outcomes.

Methods: Blood samples were collected from 74 de-novo AML patients and 16 controls. Real-time quantitative PCR (qRT-PCR) was performed to analyze BAMBI, SMAD7 and TERT expressions.

Results: BAMBI and SMAD7 expression in AML were significantly upregulated versus controls (p< 0.05). BAMBI, SMAD7 and TERT levels were significantly correlated together (p< 0.001). Kaplan-Meier analysis indicated that patients with high BAMBI, SMAD7 and TERT expression levels had markedly shorter event free survival (EFS) and overall survival (OS) time (p< 0.01). Furthermore, multivariate analysis revealed that only high BAMBI expression was an independent risk factor for OS (p= 0.001).

Conclusions: BAMBI is a novel biomarker in predicting prognosis in AML patients. Moreover, a potential interplay is found between BAMBI, SMAD7 and TERT in AML pathogenies.

Keywords: Acute myeloid leukemia; BAMBI; SMAD7; TERT; transforming growth factor-β.

MeSH terms

  • Female
  • Healthy Volunteers
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Prognosis
  • Smad7 Protein / metabolism*
  • Telomerase / metabolism*

Substances

  • BAMBI protein, human
  • Membrane Proteins
  • SMAD7 protein, human
  • Smad7 Protein
  • TERT protein, human
  • Telomerase