Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA299771 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Xenograft models represent an excellent method for expanding primary leukemias, but their ability to preserve the gene expression profile of the parent leukemia may also depend on providing microenvironmental factors that are not cross-reactive between human and mouse. Here we focused on leukemias with a CRLF2 mutation, and the ability of human TSLP to stimulate these cells.
2015-12-31 | GSE74339 | GEO
Project description:Xenograft models represent an excellent method for expanding primary leukemias, but their ability to preserve the gene expression profile of the parent leukemia may also depend on providing microenvironmental factors that are not cross-reactive between human and mouse. Here we focused on leukemias with a CRLF2 mutation, and the ability of human TSLP to stimulate these cells. Three different classes of samples were analyzed. 1) The primary leukemia sample without any culture or treatment 2) Xenograft samples (2) of the primary leukemia that were exposed to TSLP in vivo for 2 weeks, 9 weeks post-engraftment and 3) Xenograft samples (2) of the primary leukemia that were NOT exposed to TSLP in vivo for 2 weeks, 9 weeks post-engraftment.
2015-12-31 | E-GEOD-74339 | biostudies-arrayexpress
Project description:The cytokine TSLP stimulates in vitro proliferation of human fetal B cell progenitors. Genetic alterations that cause overexpression of the TSLP receptor component, CRLF2, lead to B cell acute lymphoblastic leukemia (CRLF2 B-ALL) with poor outcome. The in vivo role of TSLP in normal human B cell development and its contribution to CRLF2 B-ALL are unknown. In classic xenograft models CRLF2-mediated signaling is unlikely to be activated by mouse TSLP, based on data from engineered cellular models. Here, we show that mouse TSLP does not induce activation of the CRLF-2 downstream pathways (JAK/STAT and AKT/mTOR) that are induced by human TSLP (hTSLP) in CRLF2 B-ALL cells. Based on this, we developed a novel human-mouse xenograft model system comprised of mice that produce hTSLP (+T mice) to activate human CRLF2-mediated signaling and mice that lack hTSLP (–T mice). Normal serum levels of hTSLP were achieved in +T mice, while hTSLP was undetectable in –T mice. hTSLP produced by stroma induced JAK/STAT and AKT/mTOR pathway activation and showed functional in vivo effects on normal human B cell progenitors and primary CRLF2 B-ALL cells. Whole genome microarray of primary CRLF2 B-ALL showed an induction of mTOR regulated gene expression and preservation of TSLP responsiveness in cells expanded in +T mice as compared to –T mice.
2016-05-03 | GSE65274 | GEO
Project description:We studied the in vitro and in vivo efficacy of the HDAC inhibitor Givinostat/ITF2357 in BCP-ALL with CRLF2 rearrangements. We used BCP-ALL CRLF2- rearranged MHH-CALL4 and MUTZ5 cell lines as well as blasts from CRLF2 rearranged BCP-ALL patients and patients’ derived xenograft samples. We conclude that Givinostat may represent a novel and effective tool, in combination with current chemotherapy, to treat this subsets of ALL with poor prognosis and chemotherapy-related toxicity.
2017-03-24 | GSE77270 | GEO
Project description:WGS data set of 11 xenograft samples, Degradation of Janus kinases in CRLF2-rearranged acute lymphoblastic leukemia
| EGAD00001007570 | EGA
Project description:Chromosomal aneuploidy and translocations are hallmarks of acute lymphoblastic leukemia (ALL), but many patients lack a recurring chromosomal alteration. Here we report a recurring interstitial deletion of the pseudoautosomal region 1 of chromosomes X and Y in B-progenitor ALL that results in the expression of a novel fusion that juxtaposes the first non-coding exon of P2RY8 to the coding region of the CRLF2 (cytokine receptor like factor 2, or thymic stromal lymphopoietin receptor) gene. The P2RY8-CRLF2 fusion was identified in 7% of B-ALL cases, and was very common in ALL associated with Down syndrome (55% of cases) and was associated with the presence of JAK mutations. The P2RY8-CRLF2 fusion results in increased expression of CRLF2, a lymphoid signaling molecule that forms a heterodimeric complex with interleukin receptor 7 alpha. These findings identify a novel recurring chromosomal alteration in B-ALL, and suggest that perturbed CRLF2-mediated signaling is a key event in leukemogenesis in these cases. Profiling of tumor acquired DNA copy number alterations in 2 patients with Down syndrome associated B-progenitor acute lymphoblastic leukemia. Matched tumor and normal DNA was used for each array hybridization in each case.
2009-10-18 | E-GEOD-16724 | biostudies-arrayexpress
Project description:We analyzed the impact of CRLF2 overexpression on transcriptional and chromatin accessibility landscape in primary patient samples and cell lines in B-cell leukemia.
2023-01-01 | GSE162342 | GEO
Project description:Deregulated expression of the type I cytokine receptor, CRLF2 (CRLF2-d), is observed in 5-15% of B-cell precursor acute lymphoblastic leukaemia (BCP-ALL), is associated with activation of the JAK/STAT pathway and has an inferior outcome compared to those with good risk cytogenetics. We aimed to determine the clinical and genetic landscape of CRLF2-d ALL using genomic approaches including karyotyping, fluorescence in situ hybridisation, whole genome and whole exome sequencing. The clinical and demographic features of CRLF2-d patients were characteristic of BCP-ALL. Patients with IGH-CRLF2 were older than those with P2RY8-CRLF2 (4yrs v 14yrs, p<0.001), while the incidence of CRLF2-d among Down syndrome patients was high (31%). CRLF2-d co-occurred with established primary chromosomal rearrangements but the majority (72%) had B-other ALL. The copy number alteration (CNA) profile was similar to B-other ALL, although CRLF2-d patients harboured higher frequencies of IKZF1 (43% v 23%) and BTG1 deletions (15% v 2%). There were differences in the CNA profile between IGH-CRLF2 and P2RY8-CRLF2 patients: deletions of IKZF1 (71% v 33% p<0.001), BTG1 (31% v 9%, p=0.004) and ADD3 (46% v 13%, p=0.008). A novel gene fusion, USP9X-DDX3X was discovered in 18% of CRLF2-d ALL. Pathway analysis of the mutational profile revealed novel involvement of the focal adhesion pathway. In conclusion, CRLF2-d defines a discrete subtype of B-other ALL, characterised by a distinctive profile of cooperating abnormalities, which drive leukaemogenesis in conjunction with CRLF2-d. Although the functional relevance of many of these abnormalities are unknown, they likely activate alternative pathways, which may represent novel therapeutic targets. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic bone marrow or remission bone marrow.
2017-02-24 | GSE83272 | GEO
Project description:Chromosomal aneuploidy and translocations are hallmarks of acute lymphoblastic leukemia (ALL), but many patients lack a recurring chromosomal alteration. Here we report a recurring interstitial deletion of the pseudoautosomal region 1 of chromosomes X and Y in B-progenitor ALL that results in the expression of a novel fusion that juxtaposes the first non-coding exon of P2RY8 to the coding region of the CRLF2 (cytokine receptor like factor 2, or thymic stromal lymphopoietin receptor) gene. The P2RY8-CRLF2 fusion was identified in 7% of B-ALL cases, and was very common in ALL associated with Down syndrome (55% of cases) and was associated with the presence of JAK mutations. The P2RY8-CRLF2 fusion results in increased expression of CRLF2, a lymphoid signaling molecule that forms a heterodimeric complex with interleukin receptor 7 alpha. These findings identify a novel recurring chromosomal alteration in B-ALL, and suggest that perturbed CRLF2-mediated signaling is a key event in leukemogenesis in these cases.
2009-10-18 | GSE16724 | GEO
Project description:CRLF2-rearranged acute lymphoblastic leukemia (ALL) is associated with poor clinical outcomes. Although JAK1/2 is activated in this type of ALL, treatment with JAK1/2 inhibitors is insufficient in inhibiting cell growth and inducing apoptosis. BCL6 upregulation upon JAK inhibition may account for this insufficiency. Therefore, we compared gene expression changes of two CRLF2-rearranged ALL cell lines, MHH-CALL-4 and MUTZ-5, treated with either ruxolitinib(a JAK1/2 inhibitor), FX1(a BCL6 inhibitor), their combination, or control.
2022-07-31 | E-MTAB-10755 | biostudies-arrayexpress