Alterations of deadenylase expression in acute leukemias: evidence for poly(a)-specific ribonuclease as a potential biomarker

Acta Haematol. 2012;128(1):39-46. doi: 10.1159/000337418. Epub 2012 May 17.

Abstract

Background/aims: The degradation of mRNA is a key process in the control of gene expression correlated to anomalous cell proliferation. The rate-limiting step of mRNA degradation is the removal of the poly(A) tail by deadenylases. However, studies on deadenylase expression in cancer are limited. Herein, we analyzed the expression of several deadenylases from acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).

Methods: Clinical samples from patients diagnosed with ALL and AML were the source of leukemic cells. Extracts from leukemic and control cells were analyzed for deadenylase mRNA levels using qRT-PCR, and the protein levels of PARN and CNOT7 deadenylases using immunoblotting.

Results: RT-PCR analysis revealed altered expression for CNOT6, CNOT6L, CNOT7 and PARN deadenylases. The most significant alterations were observed for PARN and CNOT7 mRNA levels, which also reflect on the cognate protein level. Further analysis revealed that a significant amount of PARN is phosphorylated in ALL.

Conclusions: We show that the expression of several deadenylases in acute leukemias is altered. The increase of PARN expression and the alteration of its phosphorylation status indicate important regulatory events. These data suggest that the role of deadenylases as auxiliary biomarkers and therapeutic targets should be meticulously investigated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / metabolism*
  • Exoribonucleases / genetics*
  • Exoribonucleases / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Leukemia, Myeloid, Acute / enzymology
  • Leukemia, Myeloid, Acute / genetics*
  • Male
  • Middle Aged
  • Phosphorylation
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / enzymology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • RNA, Messenger / metabolism
  • Ribonucleases / genetics*
  • Ribonucleases / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Biomarkers
  • RNA, Messenger
  • Transcription Factors
  • CNOT6L protein, human
  • CNOT7 protein, human
  • Exoribonucleases
  • Ribonucleases
  • cNOT6 protein, human
  • mRNA deadenylase
  • poly(A)-specific ribonuclease