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. 2020 Aug 19;10:1422. doi: 10.3389/fonc.2020.01422

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Copyright © 2020 Dubois, Crompot, Meuleman, Bron, Lagneaux and Stamatopoulos.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Crosstalk between CLL B-cells and MSCs via soluble factors. CLL B-cells interact with MSCs by several soluble factors including cytokines (115, 117), chemokines (42, 114), and growth factors (69, 127, 128). MSCs can produce CXCL10, CXCL13, CXCL12 that binds to their respective receptor on CLL B-cells CXCR3 (118), CXCR5 (112), CXCR4 (66, 69, 75). The triggering of CXCR4/CXCL12 axis lead to the activation of several pathways including PI3K (82), MAPK (106), or STAT3 (66) leading to the survival and the migration of the leukemic cells. Interestingly, BCR stimulation induces the downregulation of CXCR4 (107), the activation of BTK (109), and the increased secretion of some cytokines. MSCs in coculture also produce IL-1β while CLL B-cells produce TNFα suggesting that coculture creates an inflammatory context (115). Figure created with BioRender.com.