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One letter change in MYD88 (L265P) keeps a B-cell survival signal permanently on; it is found in more than nine in ten Waldenström's macroglobulinaemia, most primary CNS and testicular lymphomas and a poor-risk group of DLBCL, and it predicts that BTK inhibitors will work, while a second mutation in CXCR4 predicts that they will work more slowly.
What is measured: the MYD88 L265P point mutation and, alongside it, CXCR4 nonsense or frameshift mutations (S338X the commonest) and CD79B mutations. How: allele-specific PCR or next-generation sequencing on bone marrow in Waldenström's, on tumour tissue in lymphoma, and on cerebrospinal fluid or vitreous cell-free DNA in CNS and ocular lymphoma, where it helps make a diagnosis without a brain biopsy. Frequencies: Waldenström's 90 to 95 percent, IgM MGUS 50 to 80 percent, marginal zone lymphoma under 10 percent (so a wild-type result favours marginal zone over Waldenström's), primary CNS lymphoma 60 to 80 percent with CD79B, and the MCD or cluster 5 subgroup of activated B-cell DLBCL; CXCR4 mutations are subclonal and present in 30 to 40 percent of Waldenström's. What a result changes: in Waldenström's, MYD88-mutated disease responds best to ibrutinib, zanubrutinib and acalabrutinib (ASPEN compared zanubrutinib and ibrutinib), CXCR4-mutated disease responds more slowly and less deeply with more IgM flare, favouring zanubrutinib or bendamustine-rituximab and proteasome-inhibitor regimens, and MYD88 wild-type disease does poorly on BTK inhibitors, steering to chemo-immunotherapy; in CNS lymphoma it supports BTK inhibitor trials, and in MCD DLBCL ibrutinib added to R-CHOP helped younger patients in a PHOENIX subgroup. Where it matters: Waldenström's, primary CNS lymphoma, marginal zone lymphoma and DLBCL.
In plain words · MYD88 (Myeloid differentiation primary response protein MyD88) is a gene that drives cell growth when it is altered. The public catalogues list it as a drug target, an oncogene driver and a biomarker, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Non-Hodgkin lymphoma, Leukaemia, Breast cancer and 4 more.
Showing the target this term concerns: MYD88.
Shares LymphGen and the genetic clusters of large B-cell lymphoma, MYD88, CD79b, Cell of origin (GCB vs ABC).
Shares Zanubrutinib, B-cell receptor / BTK signalling (to NF-κB), Acalabrutinib, BTK (Bruton tyrosine kinase).
Shares Zanubrutinib, B-cell receptor / BTK signalling (to NF-κB), Acalabrutinib, BTK (Bruton tyrosine kinase).
Shares MYD88, CD79b, Cell of origin (GCB vs ABC), BTK (Bruton tyrosine kinase).
Shares B-cell receptor / BTK signalling (to NF-κB), Inflammation & NF-κB, Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), Marginal zone lymphoma.
Shares B-cell receptor / BTK signalling (to NF-κB), Inflammation & NF-κB, Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), Marginal zone lymphoma.
Shares MYD88, CD79b, Cell of origin (GCB vs ABC), Primary CNS lymphoma.
Shares MYD88, CD79b, Cell of origin (GCB vs ABC), B-cell receptor / BTK signalling (to NF-κB).