English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Chemokine ligand 12(CXCL12) mediates signaling through chemokine receptor 4(CXCR4), which is essential for the homing and maintenance of Hematopoietic stem cells (HSCs) in the bone marrow. FLT3-ITD mutations enhance cell migration toward CXCL12, providing a drug resistance mechanism underlying the poor effects of FLT3-ITD antagonists. However, the mechanism by which FLT3-ITD mutations regulate the CXCL12/CXCR4 axis remains unclear. We analyzed the relationship between CXCR4 expression and the FLT3-ITD mutation in 466 patients with  de novo  AML to clarify the effect of FLT3-ITD mutations on CXCR4 expression in patients with AML. Our results indicated a positive correlation between the FLT3-ITD mutant-type allelic ratio (FLT3-ITD MR) and the relative fluorescence intensity (RFI) of CXCR4 expression in patients with AML (r = 0.588, P ≤ 0.0001). Moreover, the levels of phospho(p)-STAT5, Pim-1 and CXCR4 proteins were positively correlated with the FLT3-ITD MR, and the mRNA levels of CXCR4 and Pim-1 which has been revealed as one of the first known target genes of STAT5, were upregulated with an increasing FLT3-ITD MR(P < 0.05). Therefore, FLT3-ITD mutations upregulate the expression of CXCR4 in patients with AML, and the downstream signaling intermediates STAT5 and Pim-1 are also involved in this phenomenon and subsequently contribute to chemotherapy resistance and disease relapse in patients with AML. However, the mechanism must be confirmed in further experiments. The combination of CXCR4 antagonists and FLT3 inhibitors may improve the sensitivity of AML cells to chemotherapy and overcome drug resistance.

scientific reports

The FLT3-ITD mutation and the expression of its downstream signaling intermediates STAT5 and Pim-1 are positively correlated with CXCR4 expression in patients with acute myeloid leukemia