JAK Be Nimble: Reviewing the Development of JAK Inhibitors and JAK Inhibitor Combinations for Special Populations of Patients with Myelofibrosis

Abstract

Myelofibrosis (MF) is a myeloproliferative neoplasm hallmarked by uncontrolled blood counts, constitutional symptoms, extramedullary hematopoiesis, and an increased risk of developing acute myeloid leukemia. Janus kinase (JAK) inhibitors are the most common treatment for MF due to their ability to reduce spleen size and improve disease-related symptoms; however, JAK inhibitors are not suitable for every patient and their impact on MF is limited in several respects. Novel JAK inhibitors and JAK inhibitor combinations are emerging that aim to enhance the treatment landscape, providing deeper responses to a broader population of patients with the continued hope of providing disease modification and improving long-term outcomes. In this review, we highlight several specific areas of unmet need within MF. Subsequently, we review agents that target those areas of unmet need, focusing specifically on the JAK inhibitors, momelotinib, pacritinib, itacitinib, and NS-018 as well as JAK inhibitor combination approaches using CPI-0610, navitoclax, parsaclisib, and luspatercept.

Regulatory Mechanism of M1/M2 Macrophage Polarization in the Development of Autoimmune Diseases

“…JAK/STAT signaling pathway is an important pathway that regulates the polarization direction of macrophages. JAK (Janus kinase) kinase family plays a crucial role in the immune system and is a series of pathological Mediators of Inflammation therapeutic targets, including autoimmune diseases, COVID-19-related cytokine storms, and blood cancer [119,120]. In an in vitro experiment, it was found that peripheral blood-derived mesenchymal stem cells could secret IL-10 to induce the upregulation of JAK1/STAT3 signaling in macrophages, thereby promoting an increase in the expression of M2-type macrophages and M2-related cytokines [121].…”