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Review
. 2014 Nov;15(11):1128-38.
doi: 10.15252/embr.201438842. Epub 2014 Sep 24.

Pleiotropic roles of Notch signaling in normal, malignant, and developmental hematopoiesis in the human

Rahul Kushwah  1 , Borhane Guezguez  1 , Jung Bok Lee  1 , Claudia I Hopkins  1 , Mickie Bhatia  2
Affiliations
Review

Pleiotropic roles of Notch signaling in normal, malignant, and developmental hematopoiesis in the human

Rahul Kushwah et al. EMBO Rep. 2014 Nov.

Abstract

The Notch signaling pathway is evolutionarily conserved across species and plays an important role in regulating cell differentiation, proliferation, and survival. It has been implicated in several different hematopoietic processes including early hematopoietic development as well as adult hematological malignancies in humans. This review focuses on recent developments in understanding the role of Notch signaling in the human hematopoietic system with an emphasis on hematopoietic initiation from human pluripotent stem cells and regulation within the bone marrow. Based on recent insights, we summarize potential strategies for treatment of human hematological malignancies toward the concept of targeting Notch signaling for fate regulation.

Keywords: Notch; hematopoiesis; human pluripotent stem cells; leukemia.

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Figures

Figure 1
Figure 1. Roles of Notch signaling in human hematopoiesis and their relationships
Notch signaling plays a role in both the self-renewal and differentiation of human HSCs through direct effects on HSCs and via indirect effects through regulation of the bone marrow niche. As such, Notch plays a multifaceted role in hematological malignancies by both regulating cancer stem cells along with regulation of the transformed bone marrow niche. Modulation of Notch signaling has been utilized for improving hematopoiesis from human pluripotent stem cells (both embryonic stem cells (ES) and induced pluripotent stem cells (iPS)). Furthermore, ES/iPS offers a unique human experimental system for better understanding the roles of Notch signaling in hematopoiesis as studies involving direct modulation of Notch are not feasible in the adults.
Figure 2
Figure 2. Complex roles of Notch signaling in hematological diseases
Notch has diverse functions in hematological diseases, which ranges from roles in cancer initiation, disease progression to even tumor suppression, which is being evaluated for clinical applications for treatment of hematological diseases.
See this image and copyright information in PMC

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