MYD88
Genetic findings for MYD88 in Waldenström's Macroglobulinemia
Variants (1)
| Variant | Type | Frequency | Significance |
|---|---|---|---|
| L265P (somatic) | somatic | >90% (up to 100% by AS-PCR) | Defining molecular hallmark of WM. Gain-of-function mutation causing constitutive Myddosome assembly, BTK activation, and NF-kB-driven B-cell survival. Discovered by Treon et al. 2012 via whole-genome sequencing. |
Clinical implications
L265P (somatic)
Predicts favourable response to ibrutinib. MYD88 wild-type patients have shorter survival and poor BTK inhibitor response. Required for molecular diagnosis per ECWM consensus.
Also found in: Schnitzler syndrome (~30%), IgM-MGUS (~47%), DLBCL (ABC subtype) (~29%), Splenic marginal zone lymphoma (~6%)
Related molecules
MYD88established
Central oncogenic driver (TLR/IL-1R adaptor) — L265P gain-of-function in >90%
Related hypotheses
MYD88 L265P is the founding mutation driving constitutive NF-κB and BTK signaling in WM
90leading·85 studies
A two-hit model where MYD88 L265P provides the founding event and secondary mutations (CXCR4, ARID1A, TP53) shape disease phenotype
75leading·30 studies