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Recurrent numerical aberrations of JAK2 and deregulation of the JAK2-STAT cascade in lymphomas

Cecile Meier1, Sylvia Hoeller, Caroline Bourgau

  • 1Department of Pathology, University of Basel, Basel, Switzerland.

Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
|January 13, 2009
PubMed

Insights

Genetic aberrations targeting the Janus kinase 2 (JAK2)-signal transducers and activators of transcription (STAT) pathway are common in lymphomas. These JAK2 alterations correlate with pathway activation and impact patient outcomes in specific lymphoma subtypes.

Area of Science:

  • Hematology
  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The Janus kinase 2 (JAK2)-signal transducers and activators of transcription (STAT) pathway is crucial in hematological malignancies.
  • While JAK2 mutations are known, data on numerical and structural JAK2 aberrations in lymphoid neoplasms are limited.
  • Understanding these aberrations is key to deciphering the JAK2-STAT pathway's role in lymphomagenesis.

Purpose of the Study:

  • To investigate the molecular epidemiology of JAK2 gene aberrations (numerical and structural) in common lymphoma subtypes.
  • To assess the consecutive activation of the JAK2-STAT pathway in these lymphomas.
  • To correlate genetic aberrations with pathway activation and clinical outcomes.

Main Methods:

  • Examined 527 lymphoma cases using tissue microarrays.
  • Employed fluorescent in situ hybridization (FISH) with breakable JAK2 probes to detect numerical and structural aberrations.
  • Utilized immunohistochemistry to assess phosphorylated JAK2 (pJAK2), pSTAT3, and pSTAT5 expression.

Main Results:

  • 9p24 gains were frequent in primary mediastinal B-cell lymphomas (PMBCL, 35%), Hodgkin's lymphomas (HL, 33%), and angioimmunoblastic T-cell lymphomas (AILT, 19%).
  • 9p24 gains correlated significantly with increased pJAK2 and pSTAT3 expression.
  • Concomitant pJAK2 and pSTAT5 expression in follicular lymphomas indicated a better prognosis, while pSTAT3 in non-germinal center-like diffuse large B-cell lymphomas predicted an inferior outcome.

Conclusions:

  • Despite rare activating JAK2 mutations, numerical JAK2 aberrations are recurrent in distinct lymphoma subtypes.
  • The JAK2-STAT pathway is activated by these genetic alterations, suggesting a role in lymphomagenesis.
  • Specific JAK2-STAT pathway activation patterns can serve as prognostic markers in certain lymphomas.

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