[Frontiers in Bioscience S4, 61-73, January 1, 2012]

Structure and function of the hematopoietic cancer niche: focus on chronic lymphocytic leukemia

Jessie-F. Fecteau1,Thomas J. Kipps1

1Rebecca and John Moores Cancer Center, UCSD, La Jolla, CA 92093-0820, USA

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Disruption of healthy niches by CLL cells
3.1. Disruption of the lymphoid architecture in CLL
3.2. Impact of CLL cells on the hematopoietic niche
3.3. Impact of CLL cells on the immunologic niche
3.4. Subversion of non-neoplastic cells within the niches
3.4.1. Nurselike cells (NLCs) in CLL and other lymphomas
3.4.2. T cells in CLL and other lymphomas
3.5. The cytokine/chemokine prolife in CLL niches
3.5.1. CLL-cell factors shaping the niche
3.5.2. The cross-talk between CLL cells and NLCs
3.5.3. The cross-talk between CLL cells and mesenchymal stromal cells (MSCs)
3.5.4. The cross-talk between CLL cells and T cells
3.5.5. The cross-talk between CLL cells and follicular dendritic cells (FDCs)
4. Therapeutic strategies to disrupt the dialog between CLL cells and the supportive niche
5. Concluding remarks
6. References

1. ABSTRACT

Chronic Lymphocytic Leukemia (CLL) is a B cell malignancy characterized by the accumulation of mature monoclonal CD5-positive B cells in the blood, secondary lymphoid tissues, and marrow. The infiltration of CLL cells in lymphoid tissues is a key element of disease pathogenesis. It is in such tissues that are found the microenvironments that provide CLL cells protection from spontaneous and/or drug-induced apoptosis. CLL cells actively shape their microenvironment by producing cytokines and chemokines, and by subverting normal accessory cells to promote leukemia-cell survival, proliferation, and escape from immune detection. In this review, we discuss how CLL cells disrupt the niches required for normal hematopoiesis or immune function and subvert normal cells in the microenvironment to support neoplastic cell growth and survival.