Genomics

Dataset Information

0

Therapy resistant primitive stem cells in chronic myelogenous leukemia are characterized by low c-Kit expression and altered SCF response


ABSTRACT: Leukemia stem cells (LSC) in chronic myelogenous leukemia (CML) resist elimination with tyrosine kinase inhibitors (TKI) and persist as a source of disease recurrence. LSC populations are heterogeneous, but the most primitive, drug-resistant subsets are not well characterized. Previous studies indicate that variable cell-surface expression of the c-Kit receptor identifies heterogeneous hematopoietic stem cells (HSC) populations. We found that c-Kit expression is reduced on CML LSC compared to normal HSC. Long-term engraftment and leukemia generation capacity was restricted to low c-Kit expressing (c-KitLow) LSC, which showed increased quiescence and inflammatory gene signatures expression. The c-Kit ligand, stem cell factor (SCF), expanded normal HSC but drove maturation of CML LSC. The proportion of c-Kitlow LT-HSC was increased with TKI treatment. Supplementary SCF treatment enhanced elimination of committed but not primitive CML LT-HSC in TKI-treated mice. Low c-Kit expression identifies primitive, treatment-resistant LSC subpopulations with distinct regulatory characteristics, that are critical therapeutic targets.

ORGANISM(S): Mus musculus

PROVIDER: GSE180496 | GEO | 2022/11/29

REPOSITORIES: GEO

Similar Datasets

2019-04-02 | GSE124125 | GEO
2013-01-01 | GSE43225 | GEO
2017-01-27 | GSE84507 | GEO
2013-01-01 | E-GEOD-43225 | biostudies-arrayexpress
2021-06-16 | GSE126547 | GEO
2023-08-30 | GSE207346 | GEO
2024-01-03 | GSE212428 | GEO
2022-10-13 | GSE169750 | GEO
2010-01-01 | GSE18446 | GEO
2016-06-01 | E-GEOD-76123 | biostudies-arrayexpress