Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA237656 | ENA |
REPOSITORIES: ENA
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Project description:The BCR-ABL1 translocation product is the cause of Chronic Myeloid Leukemia (CML) and of a significant fraction of adult-onset B-Acute Lymphoblastic Leukemia (B-ALL) cases. Here we identify an essential role for gamma-catenin (junction plakoglobin) in B lineage restricted cells for the progression of B-ALL in a mouse model. The array analysis of preleukemic B cells aimed at identifying genes that explain the deficient B-ALL progression in the absence gamma-catenin. Total bone marrow cells from chimeric mice expressing or lacking gamma-catenin in the hematopoietic compartment were transduced with BCR-ABL1+ IRES GFP retrovirus before transplantation into lethally irradiated wild type recipients. Three weeks later, GFP+ (BCR-ABL1+) B220+ BP-1+ B cells were flow sorted from the bone marrow of preleukemic recipient mice. The analysis includes 3 replicates for gamma-catenin WT and 3 replicates for gamma-catenin KO BCR-ABL1+ BP1+ B cells.
2014-02-08 | E-GEOD-54793 | biostudies-arrayexpress
Project description:The BCR-ABL1 translocation product is the cause of Chronic Myeloid Leukemia (CML) and of a significant fraction of adult-onset B-Acute Lymphoblastic Leukemia (B-ALL) cases. Here we identify an essential role for gamma-catenin (junction plakoglobin) in B lineage restricted cells for the progression of B-ALL in a mouse model. The array analysis of preleukemic B cells aimed at identifying genes that explain the deficient B-ALL progression in the absence gamma-catenin. Total bone marrow cells from chimeric mice expressing or lacking gamma-catenin in the hematopoietic compartment were transduced with BCR-ABL1+ IRES GFP retrovirus before transplantation into lethally irradiated wild type recipients. Three weeks later, GFP+ (BCR-ABL1+) B220+ BP-1+ B cells were flow sorted from the bone marrow of preleukemic recipient mice.
2014-02-08 | GSE54793 | GEO
Project description:BCR-ABL1-targeting tyrosine kinase inhibitors (TKIs) have revolutionized treatment of Philadelphia chromosome-positive (Ph+) hematologic neoplasms. Nevertheless, acquired TKI resistance remains a major problem in chronic myeloid leukemia (CML), and TKIs are less effective against Ph+ B-cell acute lymphoblastic leukemia (B-ALL). GAB2, a scaffolding adaptor that binds and activates SHP2, is essential for leukemogenesis by BCR-ABL1, and a GAB2 mutant lacking SHP2 binding cannot mediate leukemogenesis. Using a genetic loss-of-function approach and bone marrow transplantation (BMT) models for CML and BCR-ABL1+ B-ALL, we show that SHP2 is required for BCR-ABL1-evoked myeloid and lymphoid neoplasia. Ptpn11 deletion impairs initiation and maintenance of CML-like myeloproliferative neoplasm, and compromises induction of BCR-ABL1+ B-ALL. SHP2, and specifically, its SH2 domains, PTP activity and C-terminal tyrosines, is essential for BCR-ABL1+, but not WT, pre-B cell proliferation. The MEK/ERK pathway is regulated by SHP2 in WT and BCR-ABL1+ pre-B cells, but is only required for the proliferation of BCR-ABL1+ cells. SHP2 is required for SRC family kinase (SFK) activation only in BCR-ABL1+ pre-B cells. RNAseq reveals distinct SHP2-dependent transcriptional programs in BCR-ABL1+ and WT pre-B cells. Our results suggest that SHP2, via SFKs and ERK, represses MXD3/4 to facilitate a MYC-dependent proliferation program in BCR-ABL1-transformed pre-B cells.
2017-06-06 | GSE99656 | GEO
Project description:Identification of beta-catenin interacting proteins via affinity purification with anti-beta-catenin antibody or IgG control in BCR-ABL1 transformed murine pre-B cells with induced beta-catenin activation via CTNNB1 exon3 fl/fl + Cre.
2025-08-13 | PXD067271 | Pride
Project description:Identification of beta-catenin interacting proteins via affinity purification with anti-beta-catenin antibody or IgG control in BCR-ABL1 transformed murine pre-B cells with induced beta-catenin activation via CTNNB1 exon3 fl/fl + Cre.
2025-08-13 | PXD067314 | Pride
Project description:Identification of beta-catenin interacting proteins via affinity purification with anti-beta-catenin antibody or IgG control in WT (NTC control) or Ikzf1/Ikzf3-KO (dual CRISPR KO) BCR-ABL1 transformed murine pre-B cells with CTNNB1 activation via a Ctnnb1 Ex3 fl/fl + Ert2Cre model.
2025-08-13 | PXD067318 | Pride
Project description:Expression of P190 and P210 BCR/ABL1 in normal human CD34(+) cells induces similar gene expression profiles and results in a STAT5-dependent expansion of the erythroid lineage The P190 and P210 BCR/ABL1 fusion genes are mainly associated with different types of hematologic malignancies, but it is presently unclear whether they are functionally different following expression in primitive human hematopoietic cells. We investigated and systematically compared the effects of retroviral P190 BCR/ABL1 and P210 BCR/ABL1 expression on cell proliferation, differentiation, and global gene expression in human CD34(+) cells from cord blood. Expression of either P190 BCR/ABL1 or P210 BCR/ABL1 resulted in expansion of erythroid cells and stimulated erythropoietin-independent burst-forming unit-erythroid colony formation. By using a lentiviral anti-signal transducer and activator of transcription 5 (STAT5) short-hairpin RNA, we found that both P190 BCR/ABL1- and P210 BCR/ABL1-induced erythroid cell expansion were STAT5-dependent. Under in vitro conditions favoring B-cell differentiation, neither P190 nor P210 BCR/ABL1-expressing cells formed detectable levels of CD19-positive cells. Gene expression profiling revealed that P190 BCR/ABL1 and P210 BCR/ABL1 induced almost identical gene expression profiles, and we identified a common set of 222 differentially expressed genes. Our data suggest that the early cellular and transcriptional effects of P190 BCR/ABL1 and P210 BCR/ABL1 expression are very similar when they are expressed in the same human progenitor cell population, and that STAT5 is an important regulator of BCR/ABL1-induced erythroid cell expansion. Keywords: global gene expression profiling, BCR/ABL1, CD34+ cord blood cells, CML, Ph+ ALL
2009-05-12 | GSE16042 | GEO
Project description:Coordinated BCR-ABL1 kinase-dependent and -independent mechanisms convert p27 from a nuclear tumor suppressor to a cytoplasmic oncogene. Persistence of oncogenic p27 functions despite effective inhibition of BCR-ABL1 may contribute to resistance to tyrosine kinase inhibitors. BCR-ABL1 induced p27 versus knockout, controlling with Empty vector p27 versus knock out
2014-10-08 | E-GEOD-59168 | biostudies-arrayexpress
Project description:BCR::ABL1 drives chronic myeloid leukemia (CML) pathology and treatment, as revealed by the success of tyrosine kinase inhibitor (TKI) therapy. However, additional poorly characterized molecular mechanisms, acting independently of BCR::ABL1, play crucial roles in CML, contributing to leukemic stem cells (LSCs) persistence, drug resistance and disease progression. Here, by combining high sensitive mass spectrometry (MS)-based phosphoproteomics with the SignalingProfiler pipeline, we obtained two signaling maps reporting the BCR::ABL1 dependent and independent pro-survival signalling mechanisms, respectively. Crucial oncogenic pathways were deregulated in resistant cells. To unbiasedly discover therapeutic vulnerabilities, we implemented the Druggability Score, a computational algorithm ranking proteins according to their inferred ability to kill resistant cells when suppressed. By this strategy, we identified a novel and unexpected role for FLT3 in BCR::ABL1 independent resistance. Remarkably, pharmacological suppression of FLT3 triggers death of both resistant cell lines and patients-derived LSCs. Finally, we propose midostaurin treatment as a therapeutic option to improve the clinical outcome of non responder patients and eradicate LSCs.
2025-05-07 | PXD056957 | Pride
Project description:This analysis focused on identifying factors that protect pre-B cells against DNA double strand break (DSB)-mediated DNA damage stress during pre-B cell differentiation. Differentiation of pre-B cells including immunoglobulin light chain gene recombination were performed by withdrawal of interleukin-7 (IL-7) from IL-7-dependent murine pre-B cells or by inhibition of the BCR-ABL1 kinase activity in BCR-ABL1-transformed pre-B cells. The BCR-ABL1 kinase inhibitor STI571 (Imatinib) was used for the inhibition of BCR-ABL1. IL-7-dependent murine pre-B cells were either cultured in IL-7 (10 ng/ml) or induced to differentiate by withdrawal of IL-7. BCR-ABL1-transformed pre-B cells were either treated with 10 µM STI571 (in absence or presence of 10 ng/ml IL-7) for 16 hours or cultured without STI571. Three samples for each condition were processed.
2010-05-27 | E-GEOD-21664 | biostudies-arrayexpress