Similar Datasets
Project description:The leukemia stem cell (LSC) populations of acute myeloid leukemia (AML) exhibit phenotypic, genetic, and functional heterogeneity that contribute to therapy failure and relapse. Progress toward understanding the mechanistic basis for therapy resistance in LSCs has been hampered by difficulties in isolating cell fractions that enrich for the entire heterogeneous population of LSCs within individual AML samples. We previously reported that CD200 gene expression is upregulated in LSC-containing AML fractions. Here, we show that CD200 is present on a greater proportion of CD45dim blasts compared with more differentiated CD45high cells in AML patient samples. In 75% (49 of 65) of AML cases we examined, CD200 was expressed on ≥10% of CD45dim blasts; of these, CD200 identified LSCs within the blast population in 9 of 10 (90%) samples tested in xenotransplantation assays. CD200+ LSCs could be isolated from CD200+ normal HSCs with the use of additional markers. Notably, CD200 expression captured both CD34- and CD34+ LSCs within individual AML samples. Analysis of highly purified CD200+ LSC-containing fractions from NPM1-mutated AMLs, which are commonly CD34-, exhibited an enrichment of primitive gene expression signatures compared with unfractionated cells. Overall, our findings support CD200 as a novel LSC marker that is able to capture the entire LSC compartment from AML patient samples, including those with NPM1 mutation.
| S-EPMC7656934 | biostudies-literature
Project description:The leukemia stem cell (LSC) populations of acute myeloid leukemia (AML) exhibit phenotypic, genetic and functional heterogeneity that contribute to therapy failure and relapse. Progress towards understanding the mechanistic basis for therapy resistance in LSCs has been hampered by difficulties in isolating cell fractions that enrich for the entire heterogeneous population of LSCs within individual AML samples. We previously reported that CD200 gene expression is upregulated in LSC-containing AML fractions. We demonstrate that CD200 is present on a greater proportion of CD45dim blasts compared to more differentiated CD45high cells in AML patient samples. In 75% of AML cases examined, CD200 was expressed on 10% of CD45dim blasts; of these, CD200 identified LSCs within the blast population in 90% of samples tested in xenotransplantation assays. Notably, CD200 expression captured both CD34- and CD34- LSCs within individual AML samples. Highly purified CD45dimCD200+ LSC-containing blasts were enriched in primitive HSC/progenitor-like signatures, while CD45dimCD200- nonengrafting blasts were enriched in myeloid-like signature. Moreover, analysis of CD45dimCD200+ blasts from NPM1-mutated AMLs also demonstrated an enrichment of primitive gene expression signatures compared to unfractionated (bulk) cells.
2020-10-10 | GSE159322 | GEO
Project description:The leukemia stem cell (LSC) populations of acute myeloid leukemia (AML) exhibit phenotypic, genetic and functional heterogeneity that contribute to therapy failure and relapse. Progress towards understanding the mechanistic basis for therapy resistance in LSCs has been hampered by difficulties in isolating cell fractions that enrich for the entire heterogeneous population of LSCs within individual AML samples. We previously reported that CD200 gene expression is upregulated in LSC-containing AML fractions. We demonstrate that CD200 is present on a greater proportion of CD45dim blasts compared to more differentiated CD45high cells in AML patient samples. In 75% of AML cases examined, CD200 was expressed on 10% of CD45dim blasts; of these, CD200 identified LSCs within the blast population in 90% of samples tested in xenotransplantation assays. Notably, CD200 expression captured both CD34- and CD34- LSCs within individual AML samples. Highly purified CD45dimCD200+ LSC-containing blasts were enriched in primitive HSC/progenitor-like signatures, while CD45dimCD200- nonengrafting blasts were enriched in myeloid-like signature. Moreover, analysis of CD45dimCD200+ blasts from NPM1-mutated AMLs also demonstrated an enrichment of primitive gene expression signatures compared to unfractionated (bulk) cells.
2020-10-10 | GSE159321 | GEO
Project description:The leukemia stem cell (LSC) populations of acute myeloid leukemia (AML) exhibit phenotypic, genetic and functional heterogeneity that contribute to therapy failure and relapse. Progress towards understanding the mechanistic basis for therapy resistance in LSCs has been hampered by difficulties in isolating cell fractions that enrich for the entire heterogeneous population of LSCs within individual AML samples. We previously reported that CD200 gene expression is upregulated in LSC-containing AML fractions. We demonstrate that CD200 is present on a greater proportion of CD45dim blasts compared to more differentiated CD45high cells in AML patient samples. In 75% of AML cases examined, CD200 was expressed on 10% of CD45dim blasts; of these, CD200 identified LSCs within the blast population in 90% of samples tested in xenotransplantation assays. Notably, CD200 expression captured both CD34- and CD34- LSCs within individual AML samples. Highly purified CD45dimCD200+ LSC-containing blasts were enriched in primitive HSC/progenitor-like signatures, while CD45dimCD200- nonengrafting blasts were enriched in myeloid-like signature. Moreover, analysis of CD45dimCD200+ blasts from NPM1-mutated AMLs also demonstrated an enrichment of primitive gene expression signatures compared to unfractionated (bulk) cells.
2020-10-10 | GSE159319 | GEO
Project description:CD200 expression marks leukemia stem cell (LSC) in human AML
| PRJNA668358 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-05-26 | GSE144984 | GEO
Project description:CD200 expression marks leukemia stem cell (LSC) in human AML part 1
| PRJNA668360 | ENA
Project description:CD200 expression marks leukemia stem cell (LSC) in human AML part 3
| PRJNA668362 | ENA
Project description:CD200 expression marks leukemia stem cells (LSC) in human AML part 2
| PRJNA668363 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-09-25 | E-GEOD-52114 | biostudies-arrayexpress