CXCR4 WHIM-like mutation

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`BIO-CXCR4-WHIM`
Type	Biomarker
Aliases	CXCR4 WHIM mutationCXCR4 mutationCXCR4-WHIMМутація CXCR4 (WHIM-подібна)
Status	reviewed 2026-04-25 \| pending_clinical_signoff
Diseases	None declared
Sources	`SRC-NCCN-BCELL-2025`

Biomarker Facts

Biomarker type	gene_mutation
Mutation details	{"functional_impact": "constitutive CXCR4 activation, persistent CXCL12 signaling", "gene": "CXCR4", "variant_type": "frameshift / nonsense in C-terminus (truncates regulatory domain)"}
Measurement	MethodPCR + Sanger sequencing OR NGS panel for CXCR4 C-terminus Unitscategorical (positive \| negative)
Related biomarkers	None declared

Notes

Cross-disease relevance: - **Waldenström / LPL** (~30%): CXCR4-WHIM-mutated patients have weaker depth of response to BTKi monotherapy (zanubrutinib, ibrutinib). May favor adding chemoimmuno (DRC) vs BTKi-only. ASPEN trial subset analysis showed differential response. - Inherited WHIM syndrome (germline): warts, hypogammaglobulinemia, immunodeficiency, myelokathexis. Direct algorithm impact in WM: weak modifier — does not yet shift primary 1L choice but informs follow-up if BTKi response suboptimal. Future: trigger early DRC switch for CXCR4-WHIM at 6-month suboptimal response.

Used By

Actionability

BMA-CXCR4-WHIM-WM - CXCR4 WHIM-like mutations co-occur in ~30-40% of MYD88-L265P Waldenström macroglobulinemi...

Algorithms

ALGO-WM-2L - ALGO-WM-2L

Biomarker

BIO-MYD88-L265P - MYD88 L265P mutation

Indications

IND-WM-2L-CARFILZOMIB-CXCR4MUT - IND-WM-2L-CARFILZOMIB-CXCR4MUT
IND-WM-2L-ZANUBRUTINIB - IND-WM-2L-ZANUBRUTINIB

Questionnaires

QUEST-WM-1L-STUB - Waldenström Macroglobulinemia / Lymphoplasmacytic Lymphoma — first line

Red flag

RF-WM-CXCR4-WHIM-MUTANT - CXCR4 WHIM-like nonsense or frameshift mutation in the C-terminal regulatory domain (e.g....