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Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma [BCR-Seq]

ABSTRACT: Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma [BCR-Seq]

PROVIDER: PRJNA784304 | ENA |

REPOSITORIES: ENA

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Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma

Project description:Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma

| PRJNA784301 | ENA

Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma [RNA-Seq]

Project description:Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma [RNA-Seq]

| PRJNA782665 | ENA

Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma [TCR-Seq]

Project description:Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma [TCR-Seq]

| PRJNA784303 | ENA

Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma [BCR-Seq]

Project description:Two percent of children with Neuroblastoma, a pediatric solid tumor of the peripheral nerve ganglia, develop Opsoclonus Myoclonus Ataxia Syndrome (OMAS), a paraneoplastic disease characterized by devastating cerebellar and brainstem-directed autoimmunity, but typically with outstanding cancer-related outcomes. Here, we compared tumor transcriptomes and tumor infiltrating T- and B-cell repertoires from a cohort of OMAS subjects with neuroblastoma to a set of controls from 13 low- and 13 high-risk non-OMAS associated neuroblastoma tumors.

2023-08-01 | GSE189741 | GEO

Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma [TCR-Seq]

2023-08-01 | GSE189742 | GEO

Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma [RNA-Seq]

2023-08-01 | GSE189367 | GEO

Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma.

Project description:Neuroblastoma is a lethal childhood solid tumor of developing peripheral nerves. Two percent of children with neuroblastoma develop opsoclonus myoclonus ataxia syndrome (OMAS), a paraneoplastic disease characterized by cerebellar and brainstem-directed autoimmunity but typically with outstanding cancer-related outcomes. We compared tumor transcriptomes and tumor-infiltrating T and B cell repertoires from 38 OMAS subjects with neuroblastoma to 26 non-OMAS-associated neuroblastomas. We found greater B and T cell infiltration in OMAS-associated tumors compared to controls and showed that both were polyclonal expansions. Tertiary lymphoid structures (TLSs) were enriched in OMAS-associated tumors. We identified significant enrichment of the major histocompatibility complex (MHC) class II allele HLA-DOB∗01:01 in OMAS patients. OMAS severity scores were associated with the expression of several candidate autoimmune genes. We propose a model in which polyclonal auto-reactive B lymphocytes act as antigen-presenting cells and drive TLS formation, thereby supporting both sustained polyclonal T cell-mediated anti-tumor immunity and paraneoplastic OMAS neuropathology.

| S-EPMC10551040 | biostudies-literature

Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-08-01 | GSE189743 | GEO

Distinct GAB2 signaling pathways are essential for myeloid and lymphoid transformation and leukemogenesis by BCR-ABL1

Project description:Tyrosine kinase inhibitors (TKIs) directed against BCR-ABL1, the product of the Philadelphia (Ph) chromosome, have revolutionized treatment of patients with chronic myeloid leukemia (CML). However, acquired resistance to TKIs is a significant clinical problem in CML, and TKI therapy is much less effective against Ph+ B-cell acute lymphoblastic leukemia (B-ALL). BCR-ABL1, via phosphorylated Tyr177, recruits the adapter GAB2 as part of a GRB2/GAB2 complex. We showed previously that GAB2 is essential for BCR-ABL1-evoked myeloid transformation in vitro. Using a genetic strategy and mouse models of CML and B-ALL, we show here that GAB2 is essential for myeloid and lymphoid leukemogenesis by BCR-ABL1. In the mouse model, recipients of BCR-ABL1-transduced Gab2-/- bone marrow failed to develop CML-like myeloproliferative neoplasia. Leukemogenesis was restored by expression of GAB2 but not by GAB2 mutants lacking binding sites for its effectors PI3K or SHP2. GAB2 deficiency also attenuated BCR-ABL1-induced B-ALL, but only the SHP2 binding site was required. The SHP2 and PI3K binding sites were differentially required for signaling downstream of GAB2. Hence, GAB2 transmits critical transforming signals from Tyr177 to PI3K and SHP2 for CML pathogenesis, whereas only the GAB2-SHP2 pathway is essential for lymphoid leukemogenesis. Given that GAB2 is dispensable for normal hematopoiesis, GAB2 and its effectors PI3K and SHP2 represent promising targets for therapy in Ph+ hematologic neoplasms. RNA-Seq expression profiling of 6 mouse bone marrow samples: 3 GAB2 WT (+/+) and 3 GAB2 NULL (-/-)

2016-01-17 | E-GEOD-75615 | biostudies-arrayexpress

Distinct GAB2 signaling pathways are essential for myeloid and lymphoid transformation and leukemogenesis by BCR-ABL1

2016-01-17 | GSE75615 | GEO