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Sabol et al. J Cancer Metastasis Treat 2021;7:20 Journal of Cancer
DOI: 10.20517/2394-4722.2021.35
Metastasis and Treatment

Review Open Access

The multifunctional role of Notch signaling in
multiple myeloma

1
Hayley M. Sabol , Jesus Delgado-Calle 1,2
1
Department of Physiology and Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
2
Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Correspondence to: Dr. Jesus Delgado-Calle, Department of Physiology and Cell Biology, University of Arkansas for Medical
Sciences, 4301 W. Markham St., #505, Biomed-2 Building, rm 208-2, Little Rock, AR 72205-7199, USA. E-mail:
JDelgadocalle@uams.edu

How to cite this article: Sabol HM, Delgado-Calle J. The multifunctional role of Notch signaling in multiple myeloma. J Cancer
Metastasis Treat 2021;7:20. https://dx.doi.org/10.20517/2394-4722.2021.35

Received: 4 Feb 2021 First Decision: 5 Mar 2021 Revised: 8 Mar 2021 Accepted: 10 Mar 2021 Available online: 14 Apr 2021

Academic Editor: Robert Coleman Copy Editor: Xi-Jun Chen Production Editor: Xi-Jun Chen

Abstract
Multiple myeloma (MM) is a hematologic cancer characterized by uncontrolled growth of malignant plasma cells
in the bone marrow and currently is incurable. The bone marrow microenvironment plays a critical role in MM. MM
cells reside in specialized niches where they interact with multiple marrow cell types, transforming the bone/bone
marrow compartment into an ideal microenvironment for the migration, proliferation, and survival of MM cells. In
addition, MM cells interact with bone cells to stimulate bone destruction and promote the development of bone
lesions that rarely heal. In this review, we discuss how Notch signals facilitate the communication between
adjacent MM cells and between MM cells and bone/bone marrow cells and shape the microenvironment to favor
MM progression and bone disease. We also address the potential and therapeutic approaches used to target
Notch signaling in MM.

Keywords: Notch, tumor microenvironment, multiple myeloma, bone, osteocytes, osteoclasts, osteoblasts, γ-
secretase inhibitors.

INTRODUCTION
Multiple myeloma (MM) is a cancer that forms in the bone marrow due to the growth and accumulation of
clonal, terminally differentiated B lymphocytes. Although considered rare, MM is the second most common
hematological cancer, accounting for 10% of all hematological cancers. The precise etiology of MM has not

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.

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