KIN-8194 blocks HCK and BTK and inhibits the growth and survival of MYD88-mutated WM and ABC DLBCL cells. (A) Representative experiments showing changes in phosphorylated HCK (pHCK^Tyr410) or (B) phosphorylated BTK (pBTK^Tyr223) levels after 1.0-hour treatment with KIN-8194 or ibrutinib at the indicated concentrations in MYD88-mutated WM (BCWM.1, MWCL-1) and ABC DLBCL (TMD-8, HBL-1) cell lines (n = 3 mice per treatment group). (C) Phosflow results for pHCK^Tyr410 and pBTK^Tyr223 in BM LPCs for MYD88-mutated WM patients after treatment with KIN-8194 or ibrutinib at indicated concentrations for 2.0 hours in the presence of whole BM mononuclear cells (n = 4). (D) Dose-response curves for MYD88^WT and MYD88^L265P cell lines after treatment with KIN-8194 or ibrutinib for 72 hours at indicated concentrations. (E) Apoptotic studies using annexin V/propidium iodide (PI) staining for primary BM LPCs and T cells from MYD88-mutated patients (n = 6) and peripheral blood B cells and T cells from healthy donors (HDs) (n = 6) after treatment with ibrutinib or KIN-8194 at indicated concentrations for 16 hours. *P < .05; **P < .01; ****P < .0001. DMSO, dimethyl sulfoxide; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; norm, normalized; RLU, relative light unit.