Bone marrow dendritic cells support the survival of chronic lymphocytic leukemia cells in a CD84 dependent manner

Avital F. Barak, Hadas Lewinsky, Michal Perpinial, Victoria Huber, Lihi Radomir, Mattias P. Kramer, Lital Sever, Yochai Wolf, Mika Shapiro, Yair Herishanu, Steffen Jung, Shirly Becker-Herman, Idit Shachar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Chronic lymphocytic leukemia (CLL) is a malignancy of mature B lymphocytes. The microenvironment of the CLL cells is a vital element in the regulation of the survival of these malignant cells. CLL cell longevity is dependent on external signals, originating from cells in their microenvironment including secreted and surface-bound factors. Dendritic cells (DCs) play an important part in tumor microenvironment, but their role in the CLL bone marrow (BM) niche has not been studied. We show here that CLL cells induce accumulation of bone marrow dendritic cells (BMDCs). Depletion of this population attenuates disease expansion. Our results show that the support of the microenvironment is partly dependent on CD84, a cell surface molecule belonging to the Signaling Lymphocyte Activating Molecule (SLAM) family of immunoreceptors. Our results suggest a novel therapeutic strategy whereby eliminating BMDCs or blocking the CD84 expressed on these cells may reduce the tumor load.

Original languageEnglish
Pages (from-to)1997-2008
Number of pages12
JournalOncogene
Volume39
Issue number9
DOIs
StatePublished - 27 Feb 2020

Funding

FundersFunder number
DKFZ-MOST
John Tracy Clinic
United States-Israel Binational Science Foundation711979
Israel Science Foundation

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