In this issue of Blood, Zhang et al~1 reported that extracellular signal-regulated kinase 2 (ERK2) substrate-binding domains have opposing roles in Janus kinase 2 V617F (JAK2V617F)-driven myeloproliferative neoplasms (MPNs). One of the domains, ERK2-docking (ERK2-D), may be a promising therapeutic target for MPNs. Conversely, the other domain, ERK2-DEF-binding pocket (ERK2-DBP), blocks progression of the disease in a mouse model. This changes the perception that simply inhibiting the catalytic activity of ERK1/2 in MPNs would be an effective therapeutic strategy.
NSTL
Amer Soc Hematology
