Waldenström macroglobulinemia

Hematol Oncol Clin North Am. 2014 Oct;28(5):945-70. doi: 10.1016/j.hoc.2014.06.003. Epub 2014 Aug 5.

Abstract

Waldenström macroglobulinemia (WM) is an IgM-secreting B-cell lymphoproliferative disorder, with strong familial predisposition. MYD88 L265P and CXCR4 WHIM mutations are common in WM and support the growth and survival of WM cells. Clinical manifestations of disease are related to both tumor cell infiltration and paraprotein production. Current treatment includes monoclonal antibodies, alkylating agents, nucleoside analogs, proteasome inhibitors, immunomodulatory drugs, and signal inhibitors. Short- and long-term toxicities should be weighed in treatment decisions with use of these agents. Elucidation of the signaling pathways involved in WM is helping to advance targeted therapeutics for WM and includes efforts directed at MYD88 and CXCR4 signaling.

Keywords: CXCR4 WHIM mutations; Lymphoproliferative disorder; MYD88 L265P; Morbidity; Treatment options; Waldenström macroglobulinemia.

Publication types

  • Review

MeSH terms

  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology*
  • Bone Marrow / metabolism
  • Bone Marrow / pathology*
  • Humans
  • Lymphoproliferative Disorders / genetics
  • Lymphoproliferative Disorders / pathology*
  • Models, Genetic
  • Mutation
  • Myeloid Differentiation Factor 88 / genetics
  • Receptors, CXCR4 / genetics
  • Signal Transduction / genetics
  • Waldenstrom Macroglobulinemia / drug therapy
  • Waldenstrom Macroglobulinemia / genetics
  • Waldenstrom Macroglobulinemia / pathology*

Substances

  • CXCR4 protein, human
  • MYD88 protein, human
  • Myeloid Differentiation Factor 88
  • Receptors, CXCR4