MYD88

Overview

MYD88 is a TLR/IL-1R adaptor and a recurrent driver in lymphoid malignancies including Waldenström macroglobulinemia and subsets of CLL.

Alterations observed in the corpus

  • Temporal ordering via PhylogicNDT placed MYD88 mutation as an early event in M-CLL PMID:35927489.
  • Mutated in 72% of PCNSLs profiled with MSK-HemePACT in the MSK ibrutinib phase II trial PMID:38995739.
  • MYD88 mutations are a key classifier for MCD DLBCL subtype in the LymphGen algorithm; classification validated using a 400-gene clinical NGS panel (MSK-IMPACT Heme) with high confidence “Core” group accuracy of 96% PMID:38497151.
  • MYD88 was recurrently mutated in DLBCL, with the L265P hotspot mutation activating NF-kB signaling in B-cell lymphomas PMID:21796119
  • MYD88 L265P and other somatic mutations were identified as recurrent drivers in diffuse large B-cell lymphoma by whole-exome sequencing of 55 tumors PMID:22343534
  • Predominantly clonal/early event in CLL; n=12 cases, clonal in 80-100% of harboring samples; mutations identified in CLL WES of 160 tumors (Broad) PMID:23415222
  • Rare mutation observed in a subset of MM patients lacking the canonical 11 driver mutations; also cited as a DLBCL driver distinguishing it from the MM mutation landscape PMID:24434212
  • In primary central nervous system lymphoma (PCNSL), MYD88 activating mutations occur in 79% (11/14) of immunocompetent cases, predominantly L265P plus rare V217F and M232T; ~2× the prevalence seen in nodal ABC-DLBCL. PMID:25991819
  • Enriched in IGHV-mutated CLL subtype in a 538-sample WES cohort (CLL8 trial) PMID:26466571
  • MYD88 was more frequently mutated in ABC DLBCL compared to GCB DLBCL; MYD88 knockout was selectively lethal in ABC DLBCL cell lines in a CRISPR screen, confirming it as a functional oncogene critical to ABC DLBCL survival; alterations in MYD88 were associated with significantly better prognosis in GCB DLBCL PMID:28985567

Cancer types (linked)

  • CLLSLL — early M-CLL driver in the integrated CLL map (n=1,148) PMID:35927489.
  • PCNSL — dominant BCR-pathway driver; MYD88-mutant PCNSLs had median PFS of 9.2 vs 2.9 months on ibrutinib (p=0.027, HR 0.39) PMID:38995739.
  • DLBCLNOS — canonical ABC-subtype driver; context for secondary CNS lymphoma in the MSK ibrutinib cohort PMID:38995739.
  • Diffuse large B-cell lymphoma (DLBCL) — key classifier for MCD subtype in LymphGen algorithm; MCD classification validated on 400-gene clinical NGS panel PMID:38497151.

Co-occurrence and mutual exclusivity

Therapeutic relevance

Open questions

  • Exploratory, underpowered biomarker association (n=46 trial) that needs prospective validation PMID:38995739.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:21796119

This page was processed by crosslinker on 2026-05-14. - PMID:22343534

This page was processed by crosslinker on 2026-05-14. - PMID:23415222

This page was processed by crosslinker on 2026-05-14. - PMID:24434212

This page was processed by crosslinker on 2026-05-14. - PMID:25991819

This page was processed by crosslinker on 2026-05-14. - PMID:26466571

This page was processed by wiki-cli on 2026-05-14. - PMID:28985567

This page was processed by wiki-cli on 2026-05-15.