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JNK2 and p38 MAPK over-expressions do not represent key events in chronic myeloid leukemia transformation

M Merkerova1, H Bruchova, R Brdicka

  • 1Institute of Hematology and Blood Transfusion, Department of Molecular Genetics, Prague, U nemocnice 1, 128 20 Prague 2, Czech Republic.

Neoplasma
|October 24, 2007
PubMed

Insights

Over-expression of JNK2 and p38 (MAP kinase family) is linked to chronic myeloid leukemia (CML). Suppressing these kinases impacts gene expression differently, but neither alone stops CML cell proliferation, suggesting other regulators are key.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • Members of the MAP kinase family, specifically JNK2 and p38, are over-expressed in chronic myeloid leukemia (CML).
  • The functional significance of this observed deregulation in CML pathogenesis remains to be fully elucidated.

Purpose of the Study:

  • To investigate the impact of JNK2 and p38 suppression on the gene expression profile of CML cell lines.
  • To determine if inhibiting JNK2 or p38 alone is sufficient to impede CML cell proliferation.

Main Methods:

  • Utilized siRNA-mediated gene silencing to specifically inhibit JNK2 and p38 in K562/KU-812 CML cell lines.
  • Employed array-based expression analyses to assess genome-wide gene expression changes post-inhibition.
  • Monitored CML cell proliferation following JNK2 or p38 gene silencing.

Main Results:

  • JNK2 depletion resulted in significant expression changes in 27 genes, including down-regulation of MSH2, MSH6, mdm2, and caspase-2, and up-regulation of MKK1, MKK6, RFC2, cytokeratins, BAD, and DR5.
  • p38 silencing led to deregulation of 20 genes, with down-regulation of caspase-10, SOD1, and Notch4, and up-regulation of caspase-2, caspase-3, CDC2, CDK4, and c-kit.
  • Neither JNK2 nor p38 inhibition significantly altered CML cell proliferation.

Conclusions:

  • JNK2 and p38 suppression affect distinct sets of genes, indicating unequal impacts of MAPK deregulation in CML cells.
  • Individual inhibition of JNK2 or p38 is insufficient to halt CML cell proliferation, suggesting the involvement of other critical upstream regulators.

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