Constitutive activation of STAT5A and STAT5B regulates IgM secretion in Waldenström's macroglobulinemia

Lucy S. Hodge, Steven C. Ziesmer, Zhi Zhang Yang, Frank J. Secreto, Anne J Novak, Stephen Maxted Ansell

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Activation of the Janus kinase family/signal transducer and activator of transcription (JAK/STAT) signaling pathway has been associated with the pathogenesis and progression of both solid and hematologic malignancies. We have detected constitutive activation of STAT5 in malignant B cells derived from patients with Waldenström's macroglobulinemia (WM). Although short hairpin RNA-mediated knockdown of the STAT5A and STAT5B isoforms did not affect cellular proliferation, loss of STAT5 significantly decreased immunoglobulin M (IgM) secretion. A similar dose-dependent inhibition of IgM secretion was observed when WM cell lines were treated with a small molecule inhibitor of STAT5. These data suggest that STAT5 is involved in regulating IgM production in WM and that inhibition of STAT5 may represent a novel therapeutic strategy for lowering IgM levels in WM patients.

Original languageEnglish (US)
Pages (from-to)1055-1058
Number of pages4
JournalBlood
Volume123
Issue number7
DOIs
StatePublished - Feb 13 2014

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Waldenstrom Macroglobulinemia
Immunoglobulin M
Chemical activation
Cells
Janus Kinases
Hematologic Neoplasms
Transcription
Transducers
Small Interfering RNA
Protein Isoforms
B-Lymphocytes
Cell Proliferation
Cell Line
Molecules
Therapeutics

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Constitutive activation of STAT5A and STAT5B regulates IgM secretion in Waldenström's macroglobulinemia. / Hodge, Lucy S.; Ziesmer, Steven C.; Yang, Zhi Zhang; Secreto, Frank J.; Novak, Anne J; Ansell, Stephen Maxted.

In: Blood, Vol. 123, No. 7, 13.02.2014, p. 1055-1058.

Research output: Contribution to journalArticle

Hodge, Lucy S. ; Ziesmer, Steven C. ; Yang, Zhi Zhang ; Secreto, Frank J. ; Novak, Anne J ; Ansell, Stephen Maxted. / Constitutive activation of STAT5A and STAT5B regulates IgM secretion in Waldenström's macroglobulinemia. In: Blood. 2014 ; Vol. 123, No. 7. pp. 1055-1058.
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