HCK is a survival determinant transactivated by mutated MYD88, and a direct target of ibrutinib.

Activating mutations in MYD88 are present in ∼95% of patients with Waldenstrom macroglobulinemia (WM), as well as other B-cell malignancies including activated B-cell (ABC) diffuse large B-cell lymphoma (DLBCL). In WM, mutated MYD88 triggers activation of Bruton tyrosine kinase (BTK). Ibrutinib,