Dataset Information

Phospho-Tyrosine analysis of the effect of CD25 KO in pre-B-ALL cells

ABSTRACT: To assess the effect of CD25 (Il2ra) knockout on signaling in pre-B leukemia, pre-B cells from CD25-floxed mouse bone marrow were grown ex-vivo with IL-7 and transformed with BCR-ABL1, before tratment with 4-OHT to induce CD25 KO. Phospho-Tyrosine proteomics was performed and differential phosphosites analysed in Cre-ERT2 vs ERT2 samples.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): B Cell, Bone Marrow

DISEASE(S): Acute Leukemia

SUBMITTER: Mark Robinson

LAB HEAD: Markus Muschen

PROVIDER: PXD036128 | Pride | 2026-02-23

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

Items per page:

1 - 5 of 33

Publications

Dynamic feedback control of oncogenic tyrosine kinase signaling in acute leukemia.

Lee Jaewoong J Sun Ruifeng R Kume Kohei K Robinson Mark E ME Cheng Zhangliang Z Cosgun Kadriye Nehir KN Ma Ning N Hurtz Christian C Geng Huimin H Luger Selina M SM Litzow Mark R MR Paietta Elisabeth E Chen Jianjun J Vaidehi Nagarajan N Müschen Markus M

Science signaling 20260210 924

CD25 is a subunit of the interleukin-2 (IL-2) receptor on T cells and natural killer (NK) cells. Acute leukemias with oncogenic tyrosine kinases often include CD25<sup>+</sup> leukemia subpopulations, which portend poor clinical outcomes for patients; however, acute leukemia cells do not respond to IL-2. Here, we identified CD25 and its phosphorylation by protein kinase Cδ (PKCδ) as central elements of a feedback loop that stabilized fluctuations in oncogenic tyrosine kinase signaling in acute l ...[more]

PMID: 41666265

Similar Datasets

Project description:Disrupting mutations of the RUNX1 gene are found in 10% of patients with myelodysplasia (MDS) and 30% of patients with acute myeloid leukemia (AML). Previous studies have revealed an increase in hematopoietic stem cells (HSCs) and multipotent progenitor (MPP) cells in conditional Runx1-knockout (KO) mice, but the molecular mechanism is unresolved. We investigated the myeloid progenitor (MP) compartment in KO mice, arguing that disruptions at the HSC/MPP level may be amplified in downstream cells. We demonstrate that the MP compartment is increased more than fivefold in Runx1 KO mice, with a prominent skewing toward megakaryocyte (Meg) progenitors. Runx1- deficient granulocyte-macrophage progenitors are characterized by increased cloning capacity, impaired development into mature cells, and HSC and Meg transcription signatures. An HSC/MPP subpopulation expressing Meg markers was also increased in Runx1-deficient mice. Rescue experiments coupled with transcriptome analysis and Runx1 DNA-binding assays demonstrated that commitment is marked by Runx1 suppression of genes encoding adherence and motility proteins (Tek, Jam3, Plxnc1, Pcdh7, and Selp) that support HSCâMeg interactions with the BM niche. In vitro assays confirmed that enforced Tek expression in HSCs/MPPs increases Meg output. Interestingly, besides this key repressor function of Runx1 to control lineage decisions and cell numbers in progenitors, our study also revealed a critical activating function in erythroblast differentiation, in addition to its known importance in Meg and granulocyte/monocyte (G/M) maturation. Thus both repressor and activator functions of Runx1 at multiple hematopoietic stages and lineages likely contribute to the tumor suppressor activity in MDS and AML. GMP were isolated either from Runx1+/+-Tg(vav-Cre) and Runx1fl/fl-Tg(vav-Cre) mice or from mice transplanted with Runx1fl/fl-Tg(vav-Cre) progenitors engineered to express GFP with RUNX1-ERt2 or ERt2. RUNX1-ERt2 activity was induced by i.p. injection of tamoxifen on 3 consecutive days prior to GMP isolation.

			Action	DRS
	200306_30738_KA_L.raw	Raw
	200306_30739_KA_L.raw	Raw
	200306_30740_KA_L.raw	Raw
	200306_30741_KA_L.raw	Raw
	200306_30742_KA_L.raw	Raw