BOF: Malignant (Non-Hodgkin Lymphoma

Which of the following amino acid substitutions in a protein’s primary structure has been associated with >90% of cases of Waldenstrom macroglobulinemia?

a) BRAF V600E

b) HFE C282Y

c) JAK2 V617F

d) MYD88 L265P

e) TP53 R248W

Answer:

d) MYD88 L265P

Explanation:

MYD88 and CXCR4 mutations of the type seen in 'WHIMS' syndrome are present in >90% and 30% to 35% of WM patients respectively and both have prognostic implications, with dual abnormalities associated with heavier bone marrow burden of disease, and wild type MYD88 with mutated CXCR4 being associated with disease refractory to ibrutinib.

Reference:

How I treat Waldenström macroglobulinemia. Treon SP. Blood Aug 2015, 126 (6) 721-732.