Emerging therapeutic paradigms to target the dysregulated Janus kinase/signal transducer and activator of transcription pathway in hematological malignancies

Abstract

Over the past decade, there has been increasing biochemical evidence that the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is aberrantly activated in malignant cells from patients with a wide spectrum of cancers of the blood and immune systems. The emerging availability of small molecule inhibitors of JAK and other signaling molecules in the JAK/STAT pathway has allowed preclinical studies validating an important role of this pathway in the pathogenesis of many hematologic malignancies, and provided motivation for new strategies for treatment of these diseases. Here, a round-table panel of experts review the current preclinical and clinical landscape of the JAK/STAT pathway in acute lymphoid and myeloid leukemias, lymphomas and myeloma, and chronic myeloid neoplasms.

Keywords::

• JAK/STAT pathway
• JAK inhibitors
• hematological malignancies

Acknowledgements

The authors wish to thank Dr. Alpa Parmar of Alpine Oncology Foundation (Switzerland) who helped to organize the JAK/STAT in hematological malignancies round-table, Incyte Corporation (USA) for the unrestricted educational support and Dr. Nicholas Sarlis (USA) for his help and insights.

Potential conflict of interest:

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.

This work was supported in part by NIH grant HL089747 to R.A.V.