Prognostic significance of PAK family kinases in acute myeloid leukemia

Cancer Gene Ther. 2020 Feb;27(1-2):30-37. doi: 10.1038/s41417-019-0090-1. Epub 2019 Mar 20.

Abstract

Acute myeloid leukemia (AML) is a clonal and heterogeneous disease characterized by a myriad of genetic defects. Genetic abnormalities are powerful prognostic factors. P21-activated kinases (PAKs) are a kind of serine/threonine protein kinases, which is regulator of plenty of oncogenic signaling pathways. The clinical and prognostic value of PAKs in AML is unclear. A total of 155 AML patients with PAK expression data from The Cancer Genome Atlas database were enrolled in this study. Eighty-four patients underwent chemotherapy only, 71 also underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the chemotherapy-only group, high PAK3 and PAK7 expression were both bound up with poor EFS and OS (all P < 0.05). However, high PAK2 expressers had better EFS and OS (all P < 0.05). Multivariate analysis demonstrated that high PAK7 expression was an adverse independent prognostic factor in patients who received chemotherapy only. PAKs have no influence in EFS and OS in patients who underwent allo-HSCT. In conclusion, high PAK2 expression is a favorable prognostic factor, as to the high expression of PAK3 and PAK7, they are poor prognostic factors, and PAK7 has better prognostic value, but their prognostic effects can be offset by allo-HSCT.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • Bone Marrow / pathology
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Leukemic
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Kaplan-Meier Estimate
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / pathology
  • Leukemia, Myeloid, Acute / therapy
  • Male
  • Middle Aged
  • Prognosis
  • Protective Factors
  • Risk Factors
  • Transplantation, Homologous
  • Young Adult
  • p21-Activated Kinases / analysis
  • p21-Activated Kinases / genetics*

Substances

  • Biomarkers, Tumor
  • PAK5 protein, human
  • PAK2 protein, human
  • PAK3 protein, human
  • p21-Activated Kinases