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MYD88
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Interpretation 14
Tier 1
MYD88
Variants
MYD88 L265P
Primary Sites
Blood
Bone Marrow
Tumor Types
Lymphoplasmacytic Lymphoma
Interpretation

MYD88 is an adaptor protein in the Toll-like receptor and interleukin 1 receptor pathway which mediates activation of NF-KB. The somatic, activating mutation in MYD88 (p.L265P) has been reported in approximately 90% of lymphoplasmacytic lymphoma (Waldenostrom's macroglobuinemia), 20-30% of cases of diffuse large B cell lymphoma (DLBCL), 10-60% of IgM MGUS, 10% of MALT lymphoma and up to 10% of chronic lymphocytic leukemia. It has not been reported in acute leukemia or multiple myeloma (including IgM myeloma). The L265P mutation increases in NFkB activity, JAK-STAT3 (Janus kinase-signal transducer and activator of transcription 3) signalling and interferon-b production. Targetted therapy using inhibitors of the different components of this pathway are at various stages of investigation. Responses to targeted therapy with Ibrutinib may vary according to MYD88 and CXCR4 mutation status according to some studies.

Citations
  1. Ngo VN, et al. Oncogenically active MYD88 mutations in human lymphoma. Nature 2011;470(7332):115-9
  2. Treon SP, et al. MYD88 L265P somatic mutation in Waldenstrom's macroglobulinemia. N Engl J Med 2012;367(9):826-33
  3. Puente XS, et al. Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia. Nature 2011;475(7354):101-5
  4. Willenbacher W, et al. Improved accuracy of discrimination between IgM multiple myeloma and Waldenstrom macroglobulinaemia by testing for MYD88 L265P mutations. Br J Haematol 2013;161(6):902-4
  5. Mori N, et al. L265P mutation of the MYD88 gene is frequent in Waldenstrom's macroglobulinemia and its absence in myeloma. PLoS One 2013;8(11):e80088
  6. Landgren O, et al. MYD88 L265P somatic mutation in IgM MGUS. N Engl J Med 2012;367(23):2255-6; author reply 2256-7
  7. Wang L, et al. SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N Engl J Med 2011;365(26):2497-506
  8. Jeelall YS, et al. Oncogenic MYD88 mutation drives Toll pathway to lymphoma. Immunol Cell Biol 2011;89(6):659-60
  9. Je EM, et al. Absence of MYD88 gene mutation in acute leukemias and multiple myelomas. Eur J Haematol 2012;88(3):273-4
  10. McIlwain H Biochemistry and neurochemistry in the 1800s: their origins in comparative animal chemistry. Essays Biochem 1990;25():197-224
  11. Kim Y, et al. CD79B and MYD88 mutations in diffuse large B-cell lymphoma. Hum Pathol 2014;45(3):556-64
  12. Martinez-Trillos A, et al. Mutations in TLR/MYD88 pathway identify a subset of young chronic lymphocytic leukemia patients with favorable outcome. Blood 2014;123(24):3790-6
  13. Treon SP, et al. Ibrutinib in previously treated Waldenstrom's macroglobulinemia. N Engl J Med 2015;372(15):1430-40
Last updated: 2020-07-24 14:53:37 UTC
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