General AML

High expression of vanin-1 can predict adverse outcomes in patients with AML

Valerio Izzi et al. from University of Oulu, Finland, corresponded in a Letter to the Editor of American Journal of Hematology, the results of their study which used a robust transcriptome analysis to identify differentially expressed genes in patients with Acute Myeloid Leukemia (AML) with or without relapse/progression at two years after conventional cytarabine and tetracycline treatment in The Cancer Genome Atlas AML Cohort (TCGA LAML) and compared it to differentially expressed genes in AML cell lines resistant versus sensitive to the treatment regimen.

The transcriptome analysis identified six differentially regulated genes including VNN1, DRGs, SPINK2, TM4SF1, BEX1, TEAD4. Of these six genes, Vanin-1 (VNN1), a glycosylphosphatidyl inositol-anchored pantetheinase that hydrolyzes pantetheine into pantotheic acid (vitamin B5), had the largest hazard ratio and lowest P value for Disease Free Survival (DFS).

Izz et al., then focused on evaluating the prognostic impact of VNN1 in AML patients. Patients were split into two groups including high (above the average VNN1 expression) and low (below the average VNN1 expression) VNN1 expression.  

The key findings were:
  • Compared to low VNN1 expression, high VNN1 expression was associated significantly with shorter DFS in the TCGA LAML (HR = 2.06, P = 0.036) cohort and shorter Event Free Survival (EFS) in both the GSE10358 (HR = 2.68, P = 0.016) and TARGET-AML (HR = 1.75, P = 0.006) cohort
  • Relapse Free Survival (RFS) in a retrospective cohort of patients was significantly longer in patients with low (n = 30) VNN1 expression compared to patients with high (n = 30) expression; P = 0.004, HR = 6.14
  • High VNN1 expression at diagnosis was associated with:
    • Higher frequency of patients with minimal residual disease and relapse or refractory
    • Lower number of patients in Complete Remission (CR) after the first and second induction cycles and during subsequent treatments
  • > 60-day mortality rate in patients with low and high VNN1 expression; 4% vs 19%, P = 0.0014
  • Compared to patients with low VNN1 expression, response rate (% of patients in CR) in patients with high VNN1 expression is reduced at the passage from the first induction cycle to the first consolidation

In summary, high VNN1 expression reduced survival and overall therapeutic success rates in AML patients thus indicating that VNN1 has prospects as a reliable marker for identifying patients with AML at risk of relapse or poor outcome.

References
  1. Izzi V. et al. Vanin 1 (VNN1) levels predict poor outcome in acute myeloid leukemia. Am J Hematol. 2017 Oct 3. DOI: 10.1002/ajh.24925. [Epub ahead of print].