title: [Waldenström's macroglobulinemia].
abstract: Waldenström macroglobulinemia (WM) is a rare and incurable B-cell neoplasm characterized by lymphoplasmacytic bone marrow infiltration and the production of serum monoclonal immunoglobulin M. Therapeutic strategies for WM should be based on individual patient and disease characteristics, including age, suitability as a candidate for autologous stem cell transplantation, hyperviscosity, and comorbidities. Rituximab forms the backbone of most regimens owing to its high efficacy and tolerability. Improved response rates to bendamustine, bortezomib, or carfilzomib in combination with rituximab and dexamethasone have been reported. For older patients, a recent phase III trial showed that oral fludarabine was more effective than chlorambucil. A Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, has also been reported as a promising agent. Through recent whole-genome sequencing in WM, MYD88L265P and CXCR4WHIM have been identified as somatic mutations. Approximately 90% of WM patients carry MYD88L265P, which activates IRAK and BTK, which in turn activate NFκB. MYD88L265P has been found to play a role in WM cell proliferation and survival. The other mutation, CXCR4WHIM, has been implicated in tumor progression and drug resistance to ibrutinib. This novel genomic landscape may alter the diagnosis, prognosis, and treatment of WM.
authors.affiliation: Division of Hematology, Saitama Medical Center, Saitama Medical University.
authors.forename: Reiko
authors.initials: R
authors.lastname: Watanabe
mesh_terms: D015894:Genome, Human; D006801:Humans; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D012307:Risk Factors; D000069283:Rituximab / Q000627:therapeutic use; D008258:Waldenstrom Macroglobulinemia / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000378:metabolism
chemical_list: C527276:CXCR4 protein, human; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D019718:Receptors, CXCR4; D000069283:Rituximab