Human FLT3 peptide

Staining for CD27 and CD201 (endothelial protein C receptor) has been recently suggested as an alternative to stem cell antigen-1 (Sca1) to identify hematopoietic stem cells in inbred mouse strains with low or nil expression of SCA1. However, whether staining for CD27 and CD201 is compatible with low fms-like tyrosine kinase 3 (FLT3) expression and the "SLAM" code defined by CD48 and CD150 to identify mouse long-term reconstituting hematopoietic stem cells has not been established. We compared the C57BL/6 strain, which expresses a high level of SCA1 on hematopoietic stem cells to non-obese diabetic severe combined immune deficient NOD.CB17-prkdc(scid)/Sz (NOD-scid) mice and NOD.CB17-prkdc(scid) il2rg(tm1Wj1)/Sz (NSG) mice which both express low to negative levels of SCA1 on hematopoietic stem cells. We demonstrate that hematopoietic stem cells are enriched within the linage-negative C-KIT+ CD27(+) CD201(+) FLT3(-) CD48CD150(+) population in serial dilution long-term competitive transplantation assays. We also make the novel observation that CD48 expression is upregulated in Lin- KIT+ progenitors from NOD-scid and NSG strains, which otherwise have very few cells expressing the CD48 ligand CD244. Finally, we report that unlike hematopoietic stem cells, SCA1 expression is similar on bone marrow endothelial and mesenchymal progenitor cells in C57BL/6, NOD-scid and NSG mice. In conclusion, we propose that the combination of Lineage, KIT, CD27, CD201, FLT3, CD48, and CD150 antigens can be used to identify long-term reconstituting hematopoietic stem cells from mouse strains expressing low levels of SCA1 on hematopoietic cells.

Background We used bioinformatic tools to dichotomize 157 non-M3 AML patients from the TCGA dataset based on the presence or absence of TP53 mutations, and screened out a key gene related to TP53 mutation for future analysis. Methods DEGs were analyzed by R package "DESeq2" and then run GSEA, GO enrichment, KEGG pathway and PPI network. Hub genes were selected out according to MCC. Log-rank (Mantel-Cox) test was used for survival analysis. Mann-Whitney U's nonparametric t test and Fisher's exact test was used for continuous and categorical variables respectively. p value< 0.05 was considered to be statistical significance. Results TNFRSF4 was final screened out as a key gene. Besides TP53 mutation (p = 0.0118), high TNFRSF4 was also associated with FLT3 mutation (p = 0.0102) and NPM1 mutation (p = 0.0024). Elevated TNFRSF4 was significantly related with intermediate (p = 0.0004) and poor (p = 0.0011) risk stratification as well as relapse statute (p = 0.0099). Patients with elevated TNFRSF4 expression had significantly shorter overall survival (median survival: 2.35 months vs. 21 months, p < 0.0001). Based on our clinical center data, TNFRSF4 expression was significantly higher in non-M3 AML patients than HDs (p = 0.0377) and MDS patients (EB-1, 2; p = 0.0017). Conclusions Elevated TNFRSF4 expression was associated with TP53, FLT3 and NPM1 mutation as well as poor clinical outcome. TNFRSF4 expression was significantly higher in non-M3 AML patients than HDs and MDS (EB-1, 2) patients. TNFRSF4 is need for future functional and mechanistic studies to investigate the role in non-M3 AML.