Similar Datasets
Project description:ATXN1-NUTM1 may define a new brain tumor entity and expand the histologic spectrum of NUTM1-rearranged neoplasia
| PRJNA576361 | ENA
Project description: Not available
| S-EPMC6937844 | biostudies-literature
Project description:NUTM1-rearrangement (NUTM1-r) represents a significant subset of infant B-ALL, particularly prevalent in cases lacking KMT2A-rearrangements (KMT2A-r). However, the underlying molecular mechanisms for the characteristic leukemia have not been fully elucidated. Our comprehensive analysis reveals that NUTM1-r infant leukemia is characterized by a unique transcriptomic and epigenetic landscape with global hypomethylation, delineating a discrete leukemia entity. Functional interrogation of the BRD9-NUTM1 fusion demonstrates its dual role in promoting B-lineage commitment while conferring leukemic stem cell properties. Strikingly, single transduction of BRD9-NUTM1 is sufficient to induce serially-transplantable pro-B-like leukemia in vivo, recapitulating key features of human NUTM1-r B-ALL, including NUTM1 overexpression, skewed B cell transcriptional programs, and low CD34 expression. Mechanistically, BRD9-NUTM1 expression gives rise to distinctive open chromatin regions with global enhancement of H3K27Ac, particularly at loci associated with Myc, NF-κB, and posterior Hoxa genes. Notably, BRD9-NUTM1 leukemic cells responded robustly to cytarabine, in contrast to the relative resistance observed in KMT2A-r leukemias. Interestingly, our findings highlight a discrepancy observed in the clinical behavior of NUTM1-r leukemias, where the transformed cells display characteristics of stemness, yet tend to lose these properties under chemotherapy due to the dependence on active transcription. Our findings delineate the unique molecular profile of NUTM1-r leukemias, suggesting opportunities for targeted therapies that exploit these specific vulnerabilities.
2026-04-22 | GSE276675 | GEO
Project description:NUTM1-rearrangement (NUTM1-r) represents a significant subset of infant B-ALL, particularly prevalent in cases lacking KMT2A-rearrangements (KMT2A-r). However, the underlying molecular mechanisms for the characteristic leukemia have not been fully elucidated. Our comprehensive analysis reveals that NUTM1-r infant leukemia is characterized by a unique transcriptomic and epigenetic landscape with global hypomethylation, delineating a discrete leukemia entity. Functional interrogation of the BRD9-NUTM1 fusion demonstrates its dual role in promoting B-lineage commitment while conferring leukemic stem cell properties. Strikingly, single transduction of BRD9-NUTM1 is sufficient to induce serially-transplantable pro-B-like leukemia in vivo, recapitulating key features of human NUTM1-r B-ALL, including NUTM1 overexpression, skewed B cell transcriptional programs, and low CD34 expression. Mechanistically, BRD9-NUTM1 expression gives rise to distinctive open chromatin regions with global enhancement of H3K27Ac, particularly at loci associated with Myc, NF-κB, and posterior Hoxa genes. Notably, BRD9-NUTM1 leukemic cells responded robustly to cytarabine, in contrast to the relative resistance observed in KMT2A-r leukemias. Interestingly, our findings highlight a discrepancy observed in the clinical behavior of NUTM1-r leukemias, where the transformed cells display characteristics of stemness, yet tend to lose these properties under chemotherapy due to the dependence on active transcription. Our findings delineate the unique molecular profile of NUTM1-r leukemias, suggesting opportunities for targeted therapies that exploit these specific vulnerabilities.
2026-04-22 | GSE276676 | GEO
Project description:NUTM1-rearrangement (NUTM1-r) defines a significant subset of B-cell acute lymphoblastic leukemia (B-ALL), particularly in infants lacking KMT2A-rearrangements (KMT2A-r), yet its underlying molecular characteristics remain poorly understood. Here, we establish that NUTM1-r leukemia is a discrete entity characterized by a unique transcriptional and epigenetic landscape, notably featuring global DNA hypomethylation, irrespective of the 5' fusion partner. Functional interrogation of NUTM1 fusions reveals a dual oncogenic role: they drive commitment towards the B-lymphoid lineage while concurrently conferring potent leukemic stem cell properties. Strikingly, expression of a representative fusion, BRD9-NUTM1, is sufficient to induce serially-transplantable prepro-B-like leukemia in vivo, faithfully recapitulating the key molecular and immunophenotypic features of human NUTM1-r B-ALL. Mechanistically, NUTM1 fusions establish an aberrant chromatin state, marked by global enhancement of H3K27 acetylation and the creation of distinctive open chromatin regions that co-opt both B-lineage and stemness-related transcriptional programs, including those involving NF-κB and posterior HoxA genes. In stark contrast to resistant KMT2A-r leukemias, NUTM1-r leukemic cells exhibit a profound sensitivity to chemotherapy. This vulnerability is mechanistically linked to the leukemia's dependence on active transcription. Our findings delineate the unique molecular profile of NUTM1-r leukemias, revealing specific vulnerabilities that rationalize their favorable clinical outcomes and suggest opportunities for modified therapeutic strategies.
2026-04-22 | GSE307522 | GEO
Project description:NUTM1-rearrangement (NUTM1-r) defines a significant subset of B-cell acute lymphoblastic leukemia (B-ALL), particularly in infants lacking KMT2A-rearrangements (KMT2A-r), yet its underlying molecular characteristics remain poorly understood. Here, we establish that NUTM1-r leukemia is a discrete entity characterized by a unique transcriptional and epigenetic landscape, notably featuring global DNA hypomethylation, irrespective of the 5' fusion partner. Functional interrogation of NUTM1 fusions reveals a dual oncogenic role: they drive commitment towards the B-lymphoid lineage while concurrently conferring potent leukemic stem cell properties. Strikingly, expression of a representative fusion, BRD9-NUTM1, is sufficient to induce serially-transplantable prepro-B-like leukemia in vivo, faithfully recapitulating the key molecular and immunophenotypic features of human NUTM1-r B-ALL. Mechanistically, NUTM1 fusions establish an aberrant chromatin state, marked by global enhancement of H3K27 acetylation and the creation of distinctive open chromatin regions that co-opt both B-lineage and stemness-related transcriptional programs, including those involving NF-κB and posterior HoxA genes. In stark contrast to resistant KMT2A-r leukemias, NUTM1-r leukemic cells exhibit a profound sensitivity to chemotherapy. This vulnerability is mechanistically linked to the leukemia's dependence on active transcription. Our findings delineate the unique molecular profile of NUTM1-r leukemias, revealing specific vulnerabilities that rationalize their favorable clinical outcomes and suggest opportunities for modified therapeutic strategies.
2026-04-22 | GSE307525 | GEO
Project description:NUTM1-rearrangement (NUTM1-r) defines a significant subset of B-cell acute lymphoblastic leukemia (B-ALL), particularly in infants lacking KMT2A-rearrangements (KMT2A-r), yet its underlying molecular characteristics remain poorly understood. Here, we establish that NUTM1-r leukemia is a discrete entity characterized by a unique transcriptional and epigenetic landscape, notably featuring global DNA hypomethylation, irrespective of the 5' fusion partner. Functional interrogation of NUTM1 fusions reveals a dual oncogenic role: they drive commitment towards the B-lymphoid lineage while concurrently conferring potent leukemic stem cell properties. Strikingly, expression of a representative fusion, BRD9-NUTM1, is sufficient to induce serially-transplantable prepro-B-like leukemia in vivo, faithfully recapitulating the key molecular and immunophenotypic features of human NUTM1-r B-ALL. Mechanistically, NUTM1 fusions establish an aberrant chromatin state, marked by global enhancement of H3K27 acetylation and the creation of distinctive open chromatin regions that co-opt both B-lineage and stemness-related transcriptional programs, including those involving NF-κB and posterior HoxA genes. In stark contrast to resistant KMT2A-r leukemias, NUTM1-r leukemic cells exhibit a profound sensitivity to chemotherapy. This vulnerability is mechanistically linked to the leukemia's dependence on active transcription. Our findings delineate the unique molecular profile of NUTM1-r leukemias, revealing specific vulnerabilities that rationalize their favorable clinical outcomes and suggest opportunities for modified therapeutic strategies.
2026-04-22 | GSE307524 | GEO
Project description:NUTM1-rearrangement (NUTM1-r) represents a significant subset of infant B-ALL, particularly prevalent in cases lacking KMT2A-rearrangements (KMT2A-r). However, the underlying molecular mechanisms for the characteristic leukemia have not been fully elucidated. Our comprehensive analysis reveals that NUTM1-r infant leukemia is characterized by a unique transcriptomic and epigenetic landscape with global hypomethylation, delineating a discrete leukemia entity. Functional interrogation of the BRD9-NUTM1 fusion demonstrates its dual role in promoting B-lineage commitment while conferring leukemic stem cell properties. Strikingly, single transduction of BRD9-NUTM1 is sufficient to induce serially-transplantable pro-B-like leukemia in vivo, recapitulating key features of human NUTM1-r B-ALL, including NUTM1 overexpression, skewed B cell transcriptional programs, and low CD34 expression. Mechanistically, BRD9-NUTM1 expression gives rise to distinctive open chromatin regions with global enhancement of H3K27Ac, particularly at loci associated with Myc, NF-κB, and posterior Hoxa genes. Notably, BRD9-NUTM1 leukemic cells responded robustly to cytarabine, in contrast to the relative resistance observed in KMT2A-r leukemias. Interestingly, our findings highlight a discrepancy observed in the clinical behavior of NUTM1-r leukemias, where the transformed cells display characteristics of stemness, yet tend to lose these properties under chemotherapy due to the dependence on active transcription. Our findings delineate the unique molecular profile of NUTM1-r leukemias, suggesting opportunities for targeted therapies that exploit these specific vulnerabilities.
2026-04-22 | GSE276679 | GEO
Project description:Although expansion of a polyglutamine tract in ATAXIN1 (ATXN1) causes Spinocerebellar ataxia type 1, the functions of wild-type ATXN1 and ATAXIN1-Like (ATXN1L) remain poorly understood. To gain insight into the function of these proteins, we generated and characterized Atxn1L-/- and Atxn1-/- ; Atxn1L-/- double mutant animals. We found that Atxn1L -/- mice have several developmental problems including hydrocephalus, omphalocoele and lung alveolarization defects. These phenotypes are more penetrant and severe in Atxn1-/- ; Atxn1L-/- mice, suggesting that Atxn1 and Atxn1L are functionally redundant. To unravel the molecular mechanism underlying the alveolarization defect in Atxn1-/- mice, we carried out microarray analyses using total lung RNA from WT, Atxn1-/- and Atxn1L-/- mice Lung tissues were dissected from 6 day old mice from either Atxn1 heterozyous intercrosses or Atxn1L heterozygous intercrosses. We collected lung tissue samples from 4 pairs of WT and Atxn1-/- amd 3 pairs of WT and Atxn1-/- mice. Total RNA extracted from the samples was subjected to microarray analysis using Affymetrix mouse gene ST 1.0 array. GSM731591-GSM731598 (Atxn1L KO and controls) and GSM731599-GSM731604 (Atxn1 KO and controls) were RMA-processed separately.
2011-11-06 | E-GEOD-29551 | biostudies-arrayexpress
Project description:Although expansion of a polyglutamine tract in ATAXIN1 (ATXN1) causes Spinocerebellar ataxia type 1, the functions of wild-type ATXN1 and ATAXIN1-Like (ATXN1L) remain poorly understood. To gain insight into the function of these proteins, we generated and characterized Atxn1L-/- and Atxn1-/- ; Atxn1L-/- double mutant animals. We found that Atxn1L -/- mice have several developmental problems including hydrocephalus, omphalocoele and lung alveolarization defects. These phenotypes are more penetrant and severe in Atxn1-/- ; Atxn1L-/- mice, suggesting that Atxn1 and Atxn1L are functionally redundant. To unravel the molecular mechanism underlying the alveolarization defect in Atxn1-/- mice, we carried out microarray analyses using total lung RNA from WT, Atxn1-/- and Atxn1L-/- mice
2011-11-06 | GSE29551 | GEO