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STAT-related transcription factors are constitutively activated in peripheral blood cells from acute leukemia

V Gouilleux-Gruart1, F Gouilleux, C Desaint

  • 1Laboratoire d'Immunologie, Centre Hospitalier Universitaire d'Amiens, France.

Blood
|March 1, 1996
PubMed

Insights

Constitutively activated signal transducers and activators of transcription (STAT) proteins were found in acute leukemia cells. This constitutive activation of STAT factors is likely involved in leukemogenesis.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Oncology

Background:

  • Cytokine-activated signal transduction pathways involve Janus kinases (JAK) and signal transducers and activators of transcription (STAT) factors.
  • Constitutive activation of these pathways is implicated in various cancers.

Purpose of the Study:

  • To investigate the activation status of STAT factors in peripheral blood cells from patients with acute leukemia.
  • To determine if STAT factors are constitutively active in vivo in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).

Main Methods:

  • Nuclear extracts from leukemia cells were analyzed using bandshift assays with specific oligonucleotide probes (beta-casein, IRF-1, ISRE).
  • Specificity of DNA-protein complex formation was confirmed using nonradioactive competitors.
  • Supershift experiments with specific antibodies identified the involved STAT proteins (STAT1, STAT3, STAT5).

Main Results:

  • Specific DNA-protein complex formation was observed with beta-casein and IRF-1 promoter probes in ALL and AML cell extracts.
  • STAT5 and STAT1-related factors were detected in ALL.
  • STAT1, STAT3, and STAT5-related proteins were identified in AML.
  • These STAT factors were active without prior cytokine stimulation, indicating constitutive activation.

Conclusions:

  • STAT factors are constitutively activated in peripheral blood cells of patients with acute leukemia (ALL and AML).
  • The constitutive activation of STAT proteins is likely a contributing factor in the development of leukemia (leukemogenesis).

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