Ptpn1 loss leads to B cell acute lymphoblastic leukemia
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE344032 | GEO | 2026/08/19
REPOSITORIES: GEO
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Project description:Ptpn1 loss leads to B cell acute lymphoblastic leukemia
| PRJNA1514124 | ENA
Project description:We report here the deep sequencing of the mRNA from peritoneal exudate cells (macrophages) purified from wildtype or Ptpn1 (PTP1B) knockout mice, either treated or untreated with IL-10. In periotenal macrophages IL-10 activates the transcription factor STAT3 to execute and anti-inflammatory gene expression programme. The tyrosine phosphatase PTPN1 targets STAT3 for dephosphorylation and leads to the deactivation of STAT3. In this study we examined the role of PTP1B in controlling the normal homeostatic level phosphorylation of STAT3 by comparing the IL-10/STAT3-mediated anti-inflammatory gene expression programme. We find that loss of PTP1B leads to an up-regulation of the activity of STAT3, both at the level of phosphorylation and also in enhanced expression of anti-inflammatory gene products. RNA-seq of wildtype and Ptpn1 (PTP1B) knockout mouse peritoneal macrophages, treated or untreated with IL-10
2014-05-12 | E-GEOD-49449 | biostudies-arrayexpress
Project description:Immune evasion by cancer cells remains a major barrier to the success of immune checkpoint blockade (ICB). Here, we identify the phosphatases PTPN1 and PTPN2 as cooperative regulators of tumor immune resistance. Dual genetic ablation or pharmacologic inhibition of PTPN1/2 enhances Type I and II interferon signaling, MHC-I and CXCL9 expression, and sensitizes tumor cells to cytotoxic T lymphocyte–mediated killing. The small-molecule inhibitor KQ791 phenocopies these effects and synergizes with anti-PD1 therapy to suppress tumor growth in murine models, including immunotherapy-refractory cancers. Mechanistically, PTPN1/2 loss augments STAT1/3/5 signaling and primes cancer cells for immunogenic cell death via IFNγ/TNFα-induced pathways. Moreover, PTPN1/2 inhibition enhances antigen release and cross-presentation, promoting robust antigen-specific CD8⁺ T cell responses. These findings highlight PTPN1&2 as essential mediators of cancer immune evasion and support their inhibition as a strategy to broaden the effectiveness of immune checkpoint blockade in solid tumors.
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Project description:The PAX5 gene is one of the cancer predisposing genes that confer high penetrance susceptibility selectively to childhood BCP-ALL. Here we report a family with a new combination of PAX5 germline and somatic variants.
2025-08-31 | E-MTAB-14349 | biostudies-arrayexpress
Project description:Gene expression data for shRNA PTPN1 knockdown vs. Non-silencing in the classical Hodgkin lymphoma-derived cell line KM-H2
2014-01-17 | GSE54157 | GEO
Project description:We report here the deep sequencing of the mRNA from peritoneal exudate cells (macrophages) purified from wildtype or Ptpn1 (PTP1B) knockout mice, either treated or untreated with IL-10. In periotenal macrophages IL-10 activates the transcription factor STAT3 to execute and anti-inflammatory gene expression programme. The tyrosine phosphatase PTPN1 targets STAT3 for dephosphorylation and leads to the deactivation of STAT3. In this study we examined the role of PTP1B in controlling the normal homeostatic level phosphorylation of STAT3 by comparing the IL-10/STAT3-mediated anti-inflammatory gene expression programme. We find that loss of PTP1B leads to an up-regulation of the activity of STAT3, both at the level of phosphorylation and also in enhanced expression of anti-inflammatory gene products.
2014-05-12 | GSE49449 | GEO
Project description:Metastasis remains the leading cause of cancer mortality, yet effective therapies are limited. While therapeutic responses are influenced by organ-specific immune microenvironments, strategies to pharmacologically modulate these niches remain poorly defined. Here, using the clinical-stage inhibitor ABBV-CLS-484 (AC484) as a chemical probe, we demonstrate that systemic PTPN1/2 inhibition remodels the pulmonary myeloid landscape, specifically activating alveolar macrophages (AMs) toward a tumoricidal state. Integrated single-cell/spatial transcriptomics and functional assays reveal that AC484 promotes AM accumulation within metastatic lesions, elevates their IFNγ production and responsiveness, and enhances their tumor-killing activity. Depletion of AMs diminishes the anti-metastatic efficacy of AC484. Mechanistically, inhibiting PTPN1/2 by AC484 amplifies IFNγ-STAT1 signaling in AMs, while disrupting this pathway impairs their tumor control capability. These findings delineate a distinct innate immune axis where PTPN1/2 acts as a molecular "brake" on AM activation, suggesting that pharmacologically unleashing tissue-resident macrophages offers a therapeutic strategy to overcome metastatic progression, particularly in microenvironments where adaptive immunity is insufficient.
2026-09-02 | GSE337931 | GEO
Project description:Gene expression data for shRNA PTPN1 knockdown vs. Non-silencing in the classical Hodgkin lymphoma-derived cell line KM-H2 A total of 4 samples were analyzed (2 Knockdown vs. 2 Non-silencing). The 2 knockdown and 2 non-silencing samples are technical replicates of each other.
2014-01-17 | E-GEOD-54157 | biostudies-arrayexpress
Project description:Metastasis remains the leading cause of cancer mortality, yet effective therapies are limited. While therapeutic responses are influenced by organ-specific immune microenvironments, strategies to pharmacologically modulate these niches remain poorly defined. Here, using the clinical-stage inhibitor ABBV-CLS-484 (AC484) as a chemical probe, we demonstrate that systemic PTPN1/2 inhibition remodels the pulmonary myeloid landscape, specifically activating alveolar macrophages (AMs) toward a tumoricidal state. Integrated single-cell/spatial transcriptomics and functional assays reveal that AC484 promotes AM accumulation within metastatic lesions, elevates their IFNγ production and responsiveness, and enhances their tumor-killing activity. Depletion of AMs diminishes the anti-metastatic efficacy of AC484. Mechanistically, inhibiting PTPN1/2 by AC484 amplifies IFNγ-STAT1 signaling in AMs, while disrupting this pathway impairs their tumor control capability. These findings delineate a distinct innate immune axis where PTPN1/2 acts as a molecular "brake" on AM activation, suggesting that pharmacologically unleashing tissue-resident macrophages offers a therapeutic strategy to overcome metastatic progression, particularly in microenvironments where adaptive immunity is insufficient.
2026-09-02 | GSE337933 | GEO
Project description:B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is caused by abnormal expansion of immature B cells. Genetic alterations can be identified in most of the BCP-ALL cases, however, some specific lesions including rearrangements of the mixed lineage leukemia (MLL) gene encoding lysine methyltransferase 2A (KMT2A) are associated with particularly poor prognosis. This MLL-rearranged subtype of leukemia poorly responds to conventional treatment and frequently undergoes a lymphoid-to-myeloid lineage switch in response to CD19-directed immunotherapy with consequent loss of B cell-specific targets for immunotherapy. Therefore, there is an urgent need to identify new targets for treatment of relapsed/refractory MLLr-BCP-ALL. Attractive targets may be found in a cell surfaceome, as membrane proteins are often expressed abnormally on cancer cells and are more accessible for therapeutics. Membrane proteins also play key roles in mediating external signaling and interactions with the microenvironment, thus being essential for cancer cell survival. RNA-based data may not always correlate with plasma membrane protein levels. Therefore, we performed the analysis of the BCP-ALL cell surfaceome by biotin labeling of plasma membrane proteins followed by tandem mass spectrometry (LC-MS/MS). This method requires high cell input and therefore was previously applied mainly to cell lines. However, the cell lines often do not fully represent primary samples due to genetic modifications and culture conditions. We have optimized the protocol of plasma membrane protein isolation and LC-MS/MS identification of patient-derived xenografts (PDXs) BCP-ALL cells. We confirmed the LC-MS/MS results by flow cytometry. Additionally, we compared the surfaceomes of PDXs BCP-ALL cells with BCP-ALL cell lines. We profiled six BCP-ALL PDXs and one cell line SEM, all with MLL translocations. In BCP-ALL PDXs we identified 1409 membrane-associated proteins, 945 of which were present in at least 3 samples. Tissue specificity analysis demonstrated that 93 of these proteins are specific for lymphoid cells, including already reported promising immunotherapeutic targets CD19, CD22, CD38, CD70, CD72, CD79A, and CD79B. The expression of selected proteins was confirmed by flow cytometry and compared to the expression on B-ALL cell lines with MLL translocation. Moreover, we identified an additional subset of proteins with potential therapeutic significance, including CD48, IL7R, ITGB7, LAIR1, LILRB1. Importantly, we observed profound differences between surfaceomes of BCP-ALL cell lines and PDX cells.
2025-06-09 | PXD058992 | Pride