title: Jak/Stat pathway in Waldenström's macroglobulinemia.
abstract: While high serum concentrations of immunoglobulin M (IgM) protein are responsible for much of the morbidity associated with Waldenström's macroglobulinemia (WM), the mechanisms controlling IgM secretion in this malignancy remain unknown. The Jak/Stat signaling pathway mediates the effects of most cytokines involved in stimulating immunoglobulin production in nonmalignant B cells. However, in many hematopoietic malignancies, cytokine-driven stimulation of the Jak/Stat pathway is hyperactive, promoting the expression of genes associated with proliferation and survival. Autocrine/paracrine signaling of cytokines present in the tumor microenvironment may lead to persistent Jak/Stat signal transduction in WM as well. Yet despite evidence implicating the Jak/Stat pathway in the pathogenesis of WM, the relationship between Jak/Stat-mediated cytokine signaling and IgM hypersecretion has not been defined. Through the use of targeted Jak/Stat inhibitors, it is now possible to examine the contribution of aberrant cytokine signaling to IgM production, potentially allowing for a more targeted approach to WM therapy.
authors: Division of Hematology, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors: Lucy S
authors: LS
authors: Hodge
authors: Stephen M
authors: SM
authors: Ansell
mesh_terms: D005260:Female; D019337:Hematologic Neoplasms / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D053612:Janus Kinases / Q000378:metabolism*; D008297:Male; D050791:STAT Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction; D008258:Waldenstrom Macroglobulinemia / Q000201:enzymology / Q000378:metabolism*
chemical_list: D050791:STAT Transcription Factors; D053612:Janus Kinases