Bcr-Abl dependent post-transcriptional activation of NME2 expression is a specific and common feature of chronic myeloid leukemia

Leuk Lymphoma. 2012 Aug;53(8):1569-76. doi: 10.3109/10428194.2012.656631. Epub 2012 Mar 1.


We have previously identified NME2 (Nm23-H2) as a tumor antigen in a patient with chronic myeloid leukemia (CML). Here we investigated the association between NME2 and Bcr-Abl. NME2 protein was highly overexpressed in the cytoplasm of peripheral blood mononuclear cells from 29/30 patients with CML at diagnosis and 10/10 patients resistant to imatinib. Protein was overexpressed in the absence of increased levels of mRNA and was limited to Bcr-Abl + populations, being absent from Bcr-Abl - patient cells, normal donors and 14/15 acute myeloid leukemia (AML) samples. Furthermore, the Bcr-Abl dependent overexpression of NME2 protein was reversed specifically by tyrosine kinase inhibitor (TKI) treatment of Ba/F3 expressing wild-type and TKI-sensitive, but not TKI-resistant, mutants of Bcr-Abl. The post-transcriptional up-regulation of the tumor antigen NME2 is therefore a common and specific property of CML closely associated with Bcr-Abl activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / metabolism
  • Benzamides
  • Cytoplasm / metabolism
  • Drug Resistance, Neoplasm
  • Female
  • Fusion Proteins, bcr-abl / metabolism*
  • Gene Expression Regulation, Leukemic*
  • Humans
  • Imatinib Mesylate
  • In Situ Hybridization, Fluorescence
  • Karyotyping
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism*
  • Leukocytes, Mononuclear / cytology
  • Male
  • Middle Aged
  • NM23 Nucleoside Diphosphate Kinases / biosynthesis*
  • Piperazines / pharmacology
  • Pyrimidines / pharmacology
  • RNA Processing, Post-Transcriptional*


  • Antigens, Neoplasm
  • Benzamides
  • NM23 Nucleoside Diphosphate Kinases
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl
  • NME2 protein, human