Prosurvival signaling driven by mutated MYD88 signaling. Mutated MYD88 triggers gene expression of hematopoietic cell kinase (HCK), a SRC family member through PAX5-mediated signaling. HCK is activated through interleukin-6 (IL-6)/IL-6 receptor (IL-6R)/gp130/JAK2/STAT3–mediated signaling triggered by autocrine and paracrine release from the surrounding microenvironment. HCK triggers BTK, spleen tyrosine kinase (SYK), and ERK1/2 signaling. BTK also triggers ERK1/2 as well as NF-κB p65–mediated prosurvival signaling. IRAK4/IRAK1 are also activated by mutated MYD88 through an HCK-independent pathway, and trigger along with BTK NF-κB p65–mediated prosurvival signaling.