Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA340164 | ENA |
REPOSITORIES: ENA
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Project description:B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is characterized by impaired B-cell maturation and poor prognosis in relapsed/refractory (R/R) cases. While CD20-targeted immunotherapies offer clinical benefit, their efficacy is limited by low and heterogeneous CD20 expression on BCP-ALL cells. In this study, we demonstrate that overexpression of wild-type IKZF1, a tumor suppressor frequently mutated in high-risk BCP-ALL, upregulates CD20 and promotes leukemic cell maturation. Using a transcriptional mimicry approach, we identified mTORC1 inhibitors as functional IKZF1 mimetics that induce CD20 expression both in vitro and in vivo. mTORC1 inhibition enhanced the antitumor efficacy of anti-CD20 monoclonal antibodies and promoted B-lineage antigen expression, including CD22, while downregulating immature markers. Mechanistically, CD20 upregulation was mediated via the AKT–FOXO1 axis, with transient AKT phosphorylation being essential for this effect. Importantly, this phenotypic shift was observed in BCP-ALL models with IKZF1 deletions, highlighting the relevance to high-risk disease. Our findings support the use of mTORC1 inhibitors to sensitize BCP-ALL cells to CD20-directed immunotherapies and suggest a broader role for these agents in enhancing antigen stability and preventing immune escape. These results provide a strong rationale for clinical evaluation of mTORC1 inhibitors as adjuncts to immunotherapy in BCP-ALL.
2026-08-14 | GSE330631 | GEO
Project description:B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells reside in the bone marrow microenvironment, where they are protected against chemotherapeutic agents. Mesenchymal stromal cells (MSCs) are key components of this supporting framework. The present study aimed to unravel whether MSCs derived from pediatric BCP-ALL patients (leukemic MSCs) differ from MSCs derived from healthy pediatric donors (control-MSCs). Therefore, we studied their gene expression profiles after 40 hours of co-culture with primary B-cell precursor acute lymphoblastic leukemia cells. MSCs were sorted using fluorescence-activated cell sorting (FACS).
2020-07-13 | GSE101454 | GEO
Project description:Whole transcriptome RNA-seq of pediatric infant (<1year of aget at diagnosis) patients affected by B-cell precursor Acute Lymphoblastic leukemia (BCP-ALL). The aim of the study is to identify fusion gene rearrangements involved in childhood leukemia, using Next Generation Sequencing (NGS)
2021-10-25 | E-MTAB-9925 | biostudies-arrayexpress
Project description:Targeted RNA-seq of pediatric infant (<1year of age at diagnosis) patients affected by B-cell precursor Acute Lymphoblastic leukemia (BCP-ALL). The aim of the study is to identify fusion gene rearrangements involved in childhood leukemia, using a custom targeted panel for RNA analysis by NGS.
2021-10-25 | E-MTAB-9971 | biostudies-arrayexpress
Project description:Characterization of therapeutic monoclonal antibodies used in the context of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). IgA2 antibodies targeting CD38 were analyzed using LC-MS/MS. Mass analysis, peptide mapping and glycoprofiling were performed to confirm sequence integrity and post-translational modifications. The analysis supports preclinical evaluation of antibody-based immunotherapies and provides insights into glycosylation relevant for effector function.
2026-06-09 | PXD066660 | Pride
Project description:Activation of the transcription factor FOXO1 contributes to multiple pathological processes. The FOXO1 inhibitor AS1842856 demonstrated strong therapeutic effects in pre-clinical models of common diseases like diabetes and anthracyclines-induced heart failure. We have previously identified FOXO1 as a B-ALL dependency and demonstrated in in vivo B-ALL models that AS1842856 increased the survival and decreased B-ALL tumor load in all critical organ compartments, but most efficiently in the CNS. Here, we interrogated the underlying molecular mechanisms by comparison of the transcriptomic effects of AS1842856 and Foxo1-KO in a B-ALL mouse model. Despite the significant similarity in sets of regulated genes, we identified GSK3B inhibition as a signature enriched only in AS1842856-treated cells. Using an in vitro kinase assay, we identified AS1842856 as a direct GSK3B inhibitor that ultimately stabilizes CTNNB1. CTNNB1-KO partially protected B-ALL cell lines from the cytotoxic effect of AS1842856. At the same time, using a chemical protein degradation model, we found that FOXO1 indeed contributes to the cytotoxic effect of AS1842856. We conclude that AS1842856 targets two known B-ALL vulnerabilities: GSK3B and FOXO1. The unique mode of action, low toxicity, and ability to penetrate the blood-brain barrier warrant further investigation of the therapeutic potential of AS1842856 in B-ALL.
2025-07-23 | GSE283254 | GEO
Project description:We found that small moleculal weight FOXO1 inhibitor has antitumor affect against BCP-ALL cell lines RS4;11 and UoCB6
2017-08-01 | GSE86067 | GEO
Project description:B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells reside in the bone marrow microenvironment, where they are protected against chemotherapeutic agents. Mesenchymal stromal cells (MSCs) are key components of this supporting framework. The present study aimed to unravel whether MSCs derived from pediatric BCP-ALL patients (leukemic MSCs) differ from MSCs derived from healthy pediatric donors (control-MSCs). Therefore, we studied their gene expression profiles.
2020-07-13 | GSE101425 | GEO
Project description:PAX5, a transcription factor essential for B-cell development, has been found as a frequent target of abnormalities in B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) cases, showing point mutations, deletions, as well as translocations with several partner genes. We identified four novel PAX5 fusion partner genes by performing a screening on BCP-ALL cases with 9p rearrangements. Copy Number Variation analysis of translocated samples showed that few significant cooperative genetic lesions are present in addition to the translocation event, suggesting that it might have a primary role in leukemogenesis.
2015-03-02 | E-MTAB-2416 | biostudies-arrayexpress
Project description:B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a heterogeneous disease that can be subdivided according to primary recurrent genetic abnormalities that are strongly associated with characteristic biological and clinical features. The detection of these abnormalities can facilitate diagnosis, risk stratification, and targeted therapy. We identified an unexpectedly high incidence of fusion genes involving ZNF384 genes, including TCF3-ZNF384, EP300-ZNF384, and CREBBP-ZNF384, in BCP-ALL of our cohort. We therefore used microarrays to evaluate the gene-expression characteristics of BCP-ALL harboring ZNF384-related fusion genes and compared with those of BCP-ALL with other types of conventional genetic abnormality.
2017-03-21 | GSE79533 | GEO