Overexpression of cancerous inhibitor ofPP2A (CIP2A) in acute myeloid leukemia

Expert Rev Hematol. 2022 May;15(5):465-471. doi: 10.1080/17474086.2022.2072825. Epub 2022 May 19.

Abstract

Background: Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy. Protein phosphatase 2A Protein phosphatase 2A (PP2A) is a major serine/threonine phosphatase and tumor suppressor that negatively regulates numerous signal transduction pathways. Cancerous inhibitor of PP2A (CIP2A) is an endogenous inhibitor of PP2A. CIP2A overexpression was shown to be a recurrent event in cytogenetic normal AML patients. The aim of the study is to evaluate the prognostic significance of CIP2A overexpression in patients with AML.

Research design and methods: The study included 174 newly diagnosed cytogenetic normal AML patients. Detection of CIP2A expression was performed using quantitative real-time PCR.

Results: CIP2A was overexpressed in 125/174 (71.8%) of patients. Correlation of CIP2A overexpression with other prognostic factors showed significant association with CD34 expression (p = 0.04). CIP2A overexpression was significantly associated with a lower rate of (complete remission) CR (p = 0.019) and shorter disease free survival (DFS) and overall survival (OS) (p < 0.001 and <0.001, respectively). In multivariate analysis, CIP2A overexpression was an independent adverse prognostic factor that negatively affected DFS and OS (p < 0.001, HR:2.8,95%CI:1.7-4.7 and p = 0.002, HR:1.8; 95%CI:1.2-2.65, respectively).

Conclusion: CIP2A overexpression is a useful prognostic marker in AML.

Keywords: Acute myeloid leukemia; CIP2A; PP2A; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantigens* / genetics
  • Autoantigens* / metabolism
  • Gene Expression
  • Humans
  • Intracellular Signaling Peptides and Proteins* / genetics
  • Intracellular Signaling Peptides and Proteins* / metabolism
  • Leukemia, Myeloid, Acute* / diagnosis
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / genetics
  • Membrane Proteins* / genetics
  • Membrane Proteins* / metabolism
  • Prognosis
  • Protein Phosphatase 2* / genetics
  • Protein Phosphatase 2* / metabolism

Substances

  • Autoantigens
  • CIP2A protein, human
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Protein Phosphatase 2