8e13ccfd-f2fd-4da7-b713-5c785ecf2484 - samples
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ABSTRACT:
PROVIDER: EGAD00001007570 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:RNAseq data set, Degradation of Janus kinases in CRLF2-rearranged acute lymphoblastic leukemia
| EGAD00001007569 | EGA
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
Project description:We evaluated the efficacy of proteolysis-targeting chimeras (PROTACs) directed against Janus kinases. Solving the structure of FDA-approved type I JAK inhibitors ruxolitinib and baricitinib bound to the JAK2 JH1 tyrosine kinase domain enabled the rational design and optimization of Cereblon (CRBN)-directed JAK PROTACs utilizing multiple derivatives of JAK inhibitors, linkers and CRBN-specific molecular glues. The resulting JAK PROTACs were evaluated for target degradation by proteomic approaches, and activity tested in CRLF2-rearranged cell line and xenograft models of ALL.
| EGAS00001005180 | EGA
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: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: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:Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia We report two novel, cryptic chromosomal abnormalities in precursor B-cell acute lymphoblastic leukemia (BCP-ALL): a translocation, either t(X;14)(p22;q32) or t(Y;14)(p11;q32), in 33 patients and an interstitial deletion, either del(X)(p22.33p22.33) or del(Y)(p11.32p11.32), in 64 patients, involving the pseudoautosomal region (PAR1) of the sex chromosomes. The incidence of these abnormalities was 5% in childhood ALL (0.8% with the translocation, 4.2% with the deletion). Patients with the translocation were older (median age 16 years), whilst the patients with the deletion were younger (median age 4 years). The two abnormalities result in deregulated expression of the cytokine receptor, cytokine receptor-like factor 2, CRLF2 (also known as thymic stromal-derived lymphopoietin receptor, TSLPR). Over-expression of CRLF2 was associated with activation of the JAK-STAT pathway in cell lines and transduced primary B-cell progenitors, sustaining their proliferation and indicating a causal role of CRLF2 over-expression in lymphoid transformation. In Down Syndrome (DS) ALL and two non DS BCP-ALL cell lines, CRLF2 deregulation was associated with mutations of the JAK2 pseudokinase domain suggesting oncogenic cooperation, as well as highlighting a link between non DS ALL and JAK2 mutations. Keyword(s): Global copy number analysis using Agilent oligonucleotide arrays DNA copy number analysis of 16 acute lymphoblastic leukaemia samples (13 diagnostic, 1 diagnostic and relapse pair and 2 cell-lines) was performed using Agilent 244K and 105K custom microarrays. These samples were hybridised against gender matched reference DNA.
2010-05-16 | E-GEOD-17165 | biostudies-arrayexpress
Project description:CRLF2 rearranged Ph-like ALL cells are driven by oncogenic cytokine receptor signaling mediated by CRLF2 and JAK2. MHH-cALL4 cells were treated with ruxolotinib (JAK2 inhibitor) to provide insight into mechanisms of drug resistance.
2020-05-28 | GSE132486 | GEO
Project description:We quantitatively evaluated H2Bub and H3K79me2 epigenetic marks genome wide in a KMT2A rearranged B lineage acute lymphoblastic leukemia cell line after treatment with bortezomib over a 6 hour time course by ChIP-Rx. We identified rapid and concordant depletion of these epigenetic marks within two hours. To look at gene expression changes, RNA sequencing was performed on KMT2A rearranged B lineage acute lymphoblastic leukemia patient samples in the presence and absence of bortezomib exposure.
2022-01-13 | GSE152816 | GEO