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Protein Tyrosine Kinases pp 115–144Cite as

JAK Kinases in Leukemias, Lymphomas, and Multiple Myeloma

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Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

The Janus kinase or just another kinase (JAK) family comprises cytoplasmic receptor-associated protein tyrosine kinases that are involved in signal transduction pathways mediated by many cytokines and cytokine-like hormones (1–4). Physiologically, these cytokines play a critical role in regulating normal cellular functions such as proliferation, survival, and differentiation. The importance of JAKs derives from the fact that they are the first proteins involved in the intracellular part of cytokine-induced signal transduction. The major signaling events downstream of JAKs are the activation of the signal transducer and activator of transcription (STAT) proteins, the Ras/Raf/mitogen-activated protein kinase (MAPK), and the phosphatidylinositol-3 kinase (PI3-K)/Akt pathways (5). Dysregulated JAK activity has pathological implications: constitutive or enhanced JAK activation has been implicated in neoplastic transformation and abnormal cell proliferation in various hematological malignancies including multiple myeloma. Therefore, JAKs represent an attractive target for the development of novel drugs that might selectively inhibit their activity. Although exciting breakthroughs have been achieved with other tyrosine kinase inhibitors, such as STI571/imatinib mesylate, pharmacological JAK inhibitors have not yet reached the clinical stage. This chapter focuses on what is known on the role of JAKs in hematological malignancies including multiple myeloma, and the development of pharmacological inhibitors for therapy of diseases associated with JAK activity.

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Authors and Affiliations

  1. Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA

    Renate Burger PhD

  2. Division of Stem Cell and Immunotherapy II, and Department of Medicine, University of Kiel, Kiel, Germany

    Martin Gramatzki MD

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  1. Renate Burger PhD
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  1. Novartis Institutes for BioMedical Research Basel, Novartis Pharma AG, Basel, Switzerland

    Doriano Fabbro PhD

  2. UCSF Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA

    Frank McCormick MD, PhD

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Burger, R., Gramatzki, M. (2006). JAK Kinases in Leukemias, Lymphomas, and Multiple Myeloma. In: Fabbro, D., McCormick, F. (eds) Protein Tyrosine Kinases. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1385/1-59259-962-1:115

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