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Overexpression of PDK2 and PDK3 reflects poor prognosis in acute myeloid leukemia

Longzhen Cui1,2,3, Zhiheng Cheng1,4, Yan Liu1

  • 1Translational Medicine Center, Huaihe Hospital of Henan University, Kaifeng, 475000, China.

Cancer Gene Therapy
|December 23, 2018
PubMed

Insights

High expression of pyruvate dehydrogenase kinase 2 (PDK2) and PDK3 are poor prognostic factors in acute myeloid leukemia (AML). However, allogeneic hematopoietic stem cell transplantation (allo-HSCT) can overcome this effect.

Area of Science:

  • Oncology
  • Biochemistry
  • Genetics

Background:

  • Acute myeloid leukemia (AML) is a cancer of immature myeloid cells.
  • Pyruvate dehydrogenase kinases (PDKs) regulate glycolysis and promote cancer cell growth.
  • The role of PDKs in AML prognosis is not well understood.

Purpose of the Study:

  • To investigate the prognostic significance of PDK family members in de novo acute myeloid leukemia (AML).
  • To determine if PDK expression impacts outcomes in AML patients.
  • To assess the effect of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on PDK-associated prognosis.

Main Methods:

  • Utilized The Cancer Genome Atlas (TCGA) database to analyze PDK gene expression in de novo AML patients without allo-HSCT (n=84).
  • Performed univariate and multivariate analyses to correlate PDK expression with event-free survival (EFS) and overall survival (OS).
  • Examined PDK expression and OS in a separate TCGA cohort of AML patients who underwent allo-HSCT (n=71).

Main Results:

  • High PDK2 expression correlated with shorter EFS in AML patients.
  • High PDK3 expression was associated with shorter OS and was an independent risk factor for both EFS and OS.
  • PDK expression did not significantly impact OS in AML patients who received allo-HSCT.

Conclusions:

  • PDK2 and PDK3, particularly PDK3, are identified as poor prognostic markers in AML.
  • The negative prognostic impact of PDK expression on survival can be mitigated by allo-HSCT.
  • Targeting PDKs may offer therapeutic potential in AML, but further research is needed.

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