These insights reveal a previously unappreciated link between HDAC1/HDAC2 as key molecular targets, the still undefined regulation of cytoplasmic-to-nuclear signaling by HDACs, and how HDACi kill JAK2V617F-positive cells from MPN patients and mice with JAK2V617F in vitro and in vivo. The gene discussed is HDAC2; the disease is myeloproliferative neoplasm.