Reverse Phase Proteomic Array Profiling of Asparagine Synthetase Expression in Newly Diagnosed Acute Myeloid Leukemia

Nisha Narayanan, Jennifer Marvin-Peek, Mohamad K. Abouelnaaj, Dhabya Majid, Bofei Wang, Brandon D. Brown, Yihua Qiu, Steven M. Kornblau, Hussein A. Abbas

Research output: Contribution to journalArticlepeer-review

Abstract

Asparaginase-based therapy is a cornerstone in acute lymphoblastic leukemia (ALL) treatment, capitalizing on the methylation status of the asparagine synthetase (ASNS) gene, which renders ALL cells reliant on extracellular asparagine. Contrastingly, ASNS expression in acute myeloid leukemia (AML) has not been thoroughly investigated, despite studies suggesting that AML with chromosome 7/7q deletions might have reduced ASNS levels. Here, we leverage reverse phase protein arrays to measure ASNS expression in 810 AML patients and assess its impact on outcomes. We find that AML with inv(16) has the lowest overall ASNS expression. While AML with deletion 7/7q had ASNS levels slightly lower than those of AML without deletion 7/7q, this observation was not significant. Low ASNS expression correlated with improved overall survival (46 versus 54 weeks, respectively, p = 0.011), whereas higher ASNS levels were associated with better response to venetoclax-based therapy. Protein correlation analysis demonstrated association between ASNS and proteins involved in methylation and DNA repair. In conclusion, while ASNS expression was not lower in patients with deletion 7/7q as initially predicted, ASNS levels were highly variable across AML patients. Further studies are needed to assess whether patients with low ASNS expression are susceptible to asparaginase-based therapy due to their inability to augment compensatory ASNS expression upon asparagine depletion.

Original languageEnglish
Pages (from-to)2495-2504
Number of pages10
JournalJournal of Proteome Research
Volume23
Issue number7
DOIs
StatePublished - 5 Jul 2024
Externally publishedYes

Keywords

  • acute myeloid leukemia (AML)
  • asparagine synthetase (ASNS)
  • chromosome 7/7q deletion
  • reverse phase proteomics array (RPPA)
  • venetoclax

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