Regulation of MAPK signaling and implications in chronic lymphocytic leukemia

Abstract

Chronic lymphocytic leukemia (CLL) is a heterogeneous B cell malignancy that still remains incurable. Recent studies have highlighted cellular and non-cellular components of the tissue microenvironment in CLL that help nurture the growth of leukemic cells by providing the necessary stimuli for their proliferation and survival. The diverse stimuli in the specialized tissue microenvironment of CLL lead to constitutive activation of several signaling pathways that includes B cell receptor signaling and the associated mitogen-activated protein kinase (MAPK) signaling. Recent findings have described aberrant activation of MAPK signaling and its interactions with other cellular signaling pathways in the pathogenesis of CLL. These studies have shed light on the deregulated molecular mechanisms contributing to hyperactivation of MAPK signaling and provided avenues for therapeutic options for aggressive CLL. In this review, we describe and discuss the current status of our understanding into the role of MAPK signaling in the pathogenesis of CLL.

Keywords:

• Word
• chronic lymphocytic leukemia
• MAPK signaling
• BCR signaling

Acknowledgements

We apologize to many authors whose work may not have been directly referenced in this review due to space constraints. This work was supported by grants from Leukemia and Lymphoma Society grant #5464-18 to A.S. and #5463-18 to V.S. This work was also supported by UNMC, GCBA Departmental Pilot Grant.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2017.1370548.