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Fig. 1 | Journal of Hematology & Oncology

Fig. 1

From: Targeting chemokines for acute lymphoblastic leukemia therapy

Fig. 1

Chemokines and their receptors’ roles in acute lymphoblastic leukemia. In osteoblastic niche, T-ALL cells are in direct, stable contact with vascular cells in the BM that produce CXCL12, while in vascular niche CXCL12 is secreted by several stromal cell types, especially CAR cells. Apart from the BM microenvironment, extramedullary organs such as the brain and spleen showed high expression of CCL19, which is involved in leukemic cells’ infiltration to such sites. CXCL12/CXCR4 triggers the activation of downstream kinases Src and ABL1 which are responsible for the phosphorylation of RhoGDI2, which released RhoA and RhoC, leading to subsequent cytoskeleton redistribution and assembly in the process of migration. CXCR4 could activate both ERK1/2 and PI3K/Akt pathways to promote the survival of leukemic blasts. In the homing of B cell progenitor ALL cells to the BM, CXCL12-mediated activation of p38MAPK was required and ZAP70 kinase can control the expression of CXCR4 and CCR7 via ERK1/2, which is correlated with CNS infiltration during T-ALL. CXCR4 could also activate RAC1 to mediate migration and engraftment of B-ALL cells in the BM or testicles. In addition, CXCR4 can induce the proliferation of T-ALL cells via Myc. CXCL10/CXCR3 axis may increase survival rate of leukemic cells during treatment through stabilizing Bcl-2 and inhibiting caspase activation. CXCL10 has also been proved to promote migration of leukemic cells via MMP9. The expression of CCR5 and CCR7 is regulated by Notch-1. CCR5 regulate leukemic cell’s proliferation and anti-apoptosis through JAK/STAT3 pathway. CCL25/CCR9 axis increase drug efflux-induced resistance by activating the binding of P-gp and ERM. It also facilitates the infiltration through RhoA-Rock-MLC and PI3K/AKT-RhoA pathway

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