Jak/stat pathway in Waldenström's macroglobulinemia

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.