title: Constitutive activation of STAT5A and STAT5B regulates IgM secretion in Waldenstrom's macroglobulinemia.
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.
authors: Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN.
authors: Lucy S
authors: LS
authors: Hodge
authors: Steven C
authors: SC
authors: Ziesmer
authors: Zhi-Zhang
authors: ZZ
authors: Yang
authors: Frank J
authors: FJ
authors: Secreto
authors: Anne J
authors: AJ
authors: Novak
authors: Stephen M
authors: SM
authors: Ansell
mesh_terms: D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D050799:STAT5 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D055571:Secretory Pathway / Q000187:drug effects / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D008258:Waldenstrom Macroglobulinemia / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
chemical_list: D007075:Immunoglobulin M; D034741:RNA, Small Interfering; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; C494095:STAT5B protein, human; D025521:Tumor Suppressor Proteins