Thus, we performed immunohistochemistry and observed that the capillary density of sinusoidal vessels was highly increased by CXCR4 antagonist with Ara-C in leukemia, showing the reconstruction of BMM with megakaryocytes in sinusoidal vessels by dual treatment.
CXCR4 chemokine receptors play an important role in leukemia proliferation, extramedullary migration, infiltration, adhesion, and resistance to chemotherapy drugs.
CXCR4 as a chemokine receptor has been found to be upregulated in cancer metastasis and has been used as a prognostic marker in various types of cancer, including leukemia, breast cancer, and prostate cancer.
To characterize the effects of PF-06747143 on leukemia progression, we used two different patient-derived xenograft (PDX) models: Patient 17<sup>CXCR4-low</sup> and P15<sup>CXCR4-high</sup> models, characterized by relatively low and high CXCR4 expression, respectively.
Next, we evaluated the CXCR4-specific peptide Pentixafor by positron emission tomography imaging in mice harboring CXCR4 positive and CXCR4 negative leukemia xenografts, and in 10 patients with active disease.
AMD3100 not only inhibits the CXCR4/SDF- 1α signal pathway but also reduces gene expression of CXCR4 and VLA-4 on leukemia cells.The drug also softens leukemia cells.
This study aimed to determine the associations between the polymorphisms located on the SDF-1 (rs1801157, G>A) and CXCR4 (rs2228014, C>T) encoding genes and susceptibility and leukemia cell dissemination in AML.
Genetic deletion of CXCR4 in murine hematopoietic progenitors abrogated leukemogenesis induced by constitutively active Notch1, whereas lack of CCR6 and CCR7, which have been shown to be involved in T cell and leukemia extravasation into the central nervous system, respectively, did not influence T cell acute lymphoblastic leukemia development.
Finally, we hypothesized that CXCR7 potentiates CXCR4 response and may contribute to the maintenance of leukemia by initiating cell recruitment to bone marrow niches that were once occupied by normal hematopoietic stem cells.
There is marked evidence that the SDF-1/CXCR4 axis is involved in the pathogenesis of leukemia and therapies that target this axis are under development.
Because chemotherapy is the mainstay of AML treatment, it was hypothesized that standard cytotoxic chemotherapeutic agents induce dynamic changes in leukemia surface CXCR4 expression, and that chemotherapy-induced upregulation of CXCR4 represents a mechanism of acquired therapeutic resistance.
The reduction in CXCR4 induced by this terpenoid was found to be cell-type specific, as its expression was also abrogated in leukemia, myeloma and breast cancer cell lines.
CXCR4 has also been found to be a prognostic marker in various types of cancer, including leukemia and breast cancer, and recent evidence has highlighted the role of CXCR4 in prostate cancer.
Given the importance of CXCR4 in cell signaling, survival, and adhesion in leukemia, the results suggest that pO(2) be considered a critical variable in conducting and interpreting studies of CXCR4 expression and regulation in leukemias.
CXCR4-Lo-transfected rat basophil leukemia-2H3 cells responded to SDF-1 with a transient rise of intracellular Ca2+ concentration and by undergoing chemotaxis.