Garima Pandey, Lucia Mazzacurati, Tegan M Rowsell, Nathan P Horvat, Narmin E Amin, Guolin Zhang, Afua A Akuffo, Christelle M Colin-Leitzinger, Eric B Haura, Andrew T Kuykendall, Ling Zhang, Pearlie K Epling-Burnette, Gary W Reuther
Myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocytosis, and primary myelofibrosis, are clonal hematopoietic neoplasms driven by mutationally activated signaling by the JAK2 tyrosine kinase. Although JAK2 inhibitors can improve MPN patients' quality of life, they do not induce complete remission as disease-driving cells persistently survive therapy. ERK activation has been highlighted as contributing to JAK2 inhibitor persistent cell survival. As ERK is a component of signaling by activated RAS proteins and by JAK2 activation, we sought to inhibit RAS activation to enhance responses to JAK2 inhibition in preclinical MPN models...
March 5, 2024: American Journal of Hematology