# MYD88 L265P and CXCR4 mutations

Source: https://onco.cc/terms/myd88-l265p/  
OnCo record `myd88-l265p` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Term
- Last checked: 2026-09-17
- Also known as: MYD88; MYD88 L265P; MYD88 mutation; MYD88-mutated; MYD88 wild-type; MYD88wt; CXCR4 mutation; CXCR4 S338X; CXCR4 WHIM-like mutation; MYD88/CXCR4 genotype; CD79B mutation; MCD subtype DLBCL; cluster 5 DLBCL

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/MYD88
- Wikipedia: https://en.wikipedia.org/wiki/MYD88

## Connected records

- targets: [BTK (Bruton tyrosine kinase)](https://onco.cc/targets/btk/), [CXCR4](https://onco.cc/targets/cxcr4/)
- drugs: [Acalabrutinib](https://onco.cc/drugs/acalabrutinib/), [Bendamustine](https://onco.cc/drugs/bendamustine/), [Ibrutinib](https://onco.cc/drugs/ibrutinib/), [Zanubrutinib](https://onco.cc/drugs/zanubrutinib/)
- terms: [Cell of origin (GCB vs ABC)](https://onco.cc/terms/cell-of-origin/), [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Next-generation sequencing (NGS)](https://onco.cc/terms/ngs/)
- cancers: [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Marginal zone lymphoma](https://onco.cc/cancers/marginal-zone-lymphoma/), [Primary CNS lymphoma](https://onco.cc/cancers/primary-cns-lymphoma/), [Waldenström macroglobulinaemia](https://onco.cc/cancers/waldenstrom/)

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