Distinct prognostic values of Annexin family members expression in acute myeloid leukemia

Clin Transl Oncol. 2019 Sep;21(9):1186-1196. doi: 10.1007/s12094-019-02045-7. Epub 2019 Jan 29.

Abstract

Background: Annexin family consist of 12 members, many of them are frequently dysregulated in human cancers. However, the diagnosis and prognosis of Annexin family expression in acute myeloid leukemia (AML) remain elusive. The aim of the present study was to assess the prognostic value of Annexin expressions in adult and pediatric AML.

Methods: GenomicScape tool was used to assess the prognostic value of the expressions of Annexin family members in a cohort of 162 adult AML patients. Quantitative reverse transcript real-time PCR (QRT-PCR) was performed to detect the ANXA2 expression level in the bone marrow-derived mononuclear cells (BMMCs) obtained from 101 pediatric AML patients and 30 controls.

Results: The results demonstrated that high mRNA expressions of ANXA2, ANXA6, and ANXA7 were significantly associated with worse prognosis, while ANXA5 was correlated with better prognosis in adult AML. QRT-PCR analysis showed that ANXA2 expression was dramatically downregulated in BMMCs of pediatric AML patients compared to controls (p < 0.0001). ROC analysis demonstrated that ANXA2 could efficiently differentiate pediatric AML patients from controls (AUC 0.872, p < 0.0001). Likewise, ANXA2 was significantly lower in AML patients with poor-risk karyotype (p = 0.048). Also, the level of ANXA2 trended to decrease in AML patients who had not achieving complete remission. Moreover, patients with lower expression of ANXA2 had higher death rate (p = 0.042) and shorter overall survival (HR 0.55, p = 0.042). Thus, these findings suggest that ANXA2 exerts poor prognostic effect on adult AML but favorable prognostic effect on pediatric AML.

Conclusions: Collectively, Annexin family members exert distinct prognostic roles in AML, and ANXA2 can be used as a biological marker for diagnosis and prognosis of pediatric AML.

Keywords: ANXA2; Acute myeloid leukemia; Annexin family; Prognostic biomarker.

MeSH terms

  • Adolescent
  • Annexins / genetics*
  • Biomarkers, Tumor / genetics*
  • Child
  • Child, Preschool
  • Computational Biology / methods*
  • Databases, Factual
  • Female
  • Gene Expression Profiling
  • Humans
  • Infant
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / mortality*
  • Leukemia, Myeloid, Acute / pathology*
  • Male
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / mortality*
  • Neoplasm Recurrence, Local / pathology*
  • Prognosis
  • Survival Rate

Substances

  • Annexins
  • Biomarkers, Tumor