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Updated: May 4, 2026

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Constitutive activation of STAT5A and STAT5B regulates IgM secretion in Waldenstrom's macroglobulinemia
Lucy S Hodge1, Steven C Ziesmer, Zhi-Zhang Yang
1Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN.
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.
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