Leukemia: Overactivation of CXCR4 drives the occurrence and development of chronic lymphocytic leukemia

CXCR4 is a G protein-coupled receptor, which can regulate the homeostasis of hematopoietic stem cells , the production of bone marrow, the production of lymphocytes, and the tendency of driving immune cells to approach its ligand CXCL12
.

CXCR4 is a G protein-coupled receptor, which can regulate the homeostasis of hematopoietic stem cells , the production of bone marrow, the production of lymphocytes, and the tendency of driving immune cells to approach its ligand CXCL12
.

CXCR4 is a G protein-coupled receptor, which can regulate the homeostasis of hematopoietic stem cells , the production of bone marrow, the production of lymphocytes, and the tendency of driving immune cells to approach its ligand CXCL12

Previous studies have shown that the binding of CXCL12 can induce a variety of G protein-dependent and independent signaling pathways, including PI3K/AKT, MAPK/ERK and PLC/Ca2+ signaling pathways
.

The abnormal CXCR4 activity is related to the occurrence and development of lymphoma and treatment resistance

Lymphoma

In this study, the researchers constructed a gain-of-function CXCR4 mutation (CXCR4 C1013G) mouse model with excessive activation of CXCR4 signaling, and identified CXCR4 as a key activator of multiple key carcinogenic pathways
.

The researchers constructed an acquired-function CXCR4 mutation (CXCR4 C1013G) mouse model with excessive activation of CXCR4 signaling, and identified CXCR4 as a key activator of multiple key carcinogenic pathways
.

The researchers constructed an acquired-function CXCR4 mutation (CXCR4 C1013G) mouse model with excessive activation of CXCR4 signaling, and identified CXCR4 as a key activator of multiple key carcinogenic pathways

Identification of the transcriptional characteristics of CXCR4 overactivation signal

Identification of the transcriptional characteristics of CXCR4 overactivation signal

Further studies have found that the over-activated CXCR4 signal can cooperate with TCL1 to induce a unique oncogenic transcription program in B cells, which is characterized by the activation of PLK1/FOXM1 related signaling pathways
.

Correspondingly, Eμ-TCL1 CXCR4 C1013G B cells showed an enrichment of relevant transcription characteristics in patients with Richter syndrome, which is an aggressive transformation state of CLL

It is worth noting that in aggressive lymphoma, the activation of MYC is associated with increased expression of CXCR4
.

Consistently, in the Eμ-Myc mouse model (an aggressive B-cell carcinoma model), the additional over-activated CXCR4 signal does not affect survival

Co-activation of CXCR4 and TCL1 mediates a unique oncogenic transcription program in B cells

Co-activation of CXCR4 and TCL1 mediates a unique oncogenic transcription program in B cells

All in all, the results of this study indicate that excessive activation of CXCR4 is a common driver of aggressive lymphoma phenotype
.

Excessive activation of CXCR4 is a common driver of aggressive lymphoma phenotype
.

Excessive activation of CXCR4 is a common driver of aggressive lymphoma phenotype

CXCR4 hyperactivation cooperates with TCL1 in CLL development and aggressiveness.

 

Leave a message here