JAKs to STATs: A tantalizing therapeutic target in acute myeloid leukemia.

Overview

The Janus Associated Kinase-Signal Transducers and Activators of Transcription (JAK-STAT) signaling pathway plays a pivotal role in hematopoietic growth factor signaling. Hyperactive JAK-STAT signaling is implicated in the pathogenesis of myeloid malignancies, including acute myeloid leukemia (AML). The significant headway in understanding the biology of AML has led to an explosion of novel therapeutics with mechanistic rationale for the treatment of newly diagnosed and relapsed/refractory (R/R) AML. Most importantly, selective targeting of the JAK-STAT pathway has proven to be an effective therapeutic strategy in myeloproliferative neoplasms and is also being evaluated in related myeloid malignancies, including AML. This comprehensive review will focus on the apparent and evolving potential of JAK-STAT pathway inhibition in AML with emphasis on JAK inhibitors, highlighting both success and failure with this experimental approach in the clinic, and identifying rationally based combinatorial approaches.