miR-126 identifies a quiescent and chemo-resistant human B-ALL cell subset that correlates with minimal residual disease.
Details
Serval ID
serval:BIB_27B8A2CE71A6
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
miR-126 identifies a quiescent and chemo-resistant human B-ALL cell subset that correlates with minimal residual disease.
Journal
Leukemia
ISSN
1476-5551 (Electronic)
ISSN-L
0887-6924
Publication state
Published
Issued date
10/2023
Peer-reviewed
Oui
Volume
37
Number
10
Pages
1994-2005
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Abstract
Complete elimination of B-cell acute lymphoblastic leukemia (B-ALL) by a risk-adapted primary treatment approach remains a clinical key objective, which fails in up to a third of patients. Recent evidence has implicated subpopulations of B-ALL cells with stem-like features in disease persistence. We hypothesized that microRNA-126, a core regulator of hematopoietic and leukemic stem cells, may resolve intratumor heterogeneity in B-ALL and uncover therapy-resistant subpopulations. We exploited patient-derived xenograft (PDX) models with B-ALL cells transduced with a miR-126 reporter allowing the prospective isolation of miR-126(high) cells for their functional and transcriptional characterization. Discrete miR-126(high) populations, often characterized by MIR126 locus demethylation, were identified in 8/9 PDX models and showed increased repopulation potential, in vivo chemotherapy resistance and hallmarks of quiescence, inflammation and stress-response pathway activation. Cells with a miR-126(high) transcriptional profile were identified as distinct disease subpopulations by single-cell RNA sequencing in diagnosis samples from adult and pediatric B-ALL. Expression of miR-126 and locus methylation were tested in several pediatric and adult B-ALL cohorts, which received standardized treatment. High microRNA-126 levels and locus demethylation at diagnosis associate with suboptimal response to induction chemotherapy (MRD > 0.05% at day +33 or MRD+ at day +78).
Pubmed
Web of science
Create date
19/09/2023 14:21
Last modification date
13/10/2023 6:01