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Chromothripsis orchestrates leukemic transformation in blast phase MPN through targetable amplification of DYRK1A

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE240407 | GEO | 2025/03/05

REPOSITORIES: GEO

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Chromothripsis orchestrates leukemic transformation in blast phase MPN through targetable amplification of DYRK1A [ATAC]

Project description:Investigating the impact of chr21 amplification in primary patient Lin-Cd34+ cells

2025-03-06 | GSE240405 | GEO

Chromothripsis orchestrates leukemic transformation in blast phase MPN through targetable amplification of DYRK1A [RNA]

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Chromothripsis-associated chromosome 21 amplification orchestrates transformation to blast phase MPN through targetable overexpression of DYRK1A

Project description:To investigate the effect of chr21amp on cell differentiation, we performed droplet-based, high-throughput single-cell RNA-seq on Lin-CD34+ cells and total mononuclear cells.

2025-03-27 | GSE292030 | GEO

Chromothripsis orchestrates leukemic transformation in blast phase MPN through targetable amplification of DYRK1A

Project description:Chromothripsis orchestrates leukemic transformation in blast phase MPN through targetable amplification of DYRK1A

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Chromothripsis orchestrates leukemic transformation in blast phase MPN through targetable amplification of DYRK1A [RNA]

Project description:Chromothripsis orchestrates leukemic transformation in blast phase MPN through targetable amplification of DYRK1A [RNA]

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Chromothripsis orchestrates leukemic transformation in blast phase MPN through targetable amplification of DYRK1A [ATAC]

Project description:Chromothripsis orchestrates leukemic transformation in blast phase MPN through targetable amplification of DYRK1A [ATAC]

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Chromothripsis-associated chromosome 21 amplification orchestrates transformation to blast phase MPN through targetable overexpression of DYRK1A

Project description:Chromothripsis-associated chromosome 21 amplification orchestrates transformation to blast phase MPN through targetable overexpression of DYRK1A

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Genetic factors rather than blast reduction determine outcomes of allogeneic HCT in BCR-ABL-negative MPN in blast phase.

Project description:There is a limited understanding of the clinical and molecular factors associated with outcomes of hematopoietic cell transplantation (HCT) in patients with BCR-ABL-negative myeloproliferative neoplasms in blast phase (MPN-BP). Using the Center for International Blood and Marrow Transplant Research database, we evaluated HCT outcomes in 177 patients with MPN-BP. Ninety-five (54%) had sufficient DNA for targeted next-generation sequencing of 49 genes clinically relevant in hematologic malignancies. At 5 years, overall survival (OS), cumulative incidence of relapse, and nonrelapse mortality of the study cohort was 18%, 61%, and 25%, respectively. In a multivariable model, poor-risk cytogenetics was associated with inferior OS (hazard ratio [HR], 1.71; 95% CI, 1.21-2.41) due to increased relapse (HR, 1.93; 95% CI, 1.32-2.82). Transplants using mobilized peripheral blood (PB) were associated with better OS (HR, 0.60; 95% CI, 0.38-0.96). No difference in outcomes was observed in patients undergoing HCT with PB/BM blasts <5% vs those with active leukemia. Among the 95 patients with molecular data, mutation of TP53, present in 23%, was the only genetic alteration associated with outcomes. In a multivariate model, TP53-mutant patients had inferior OS (HR, 1.99; 95% CI, 1.14-3.49) and increased incidence of relapse (HR, 2.59; 95% CI, 1.41-4.74). There were no differences in the spectrum of gene mutations, number of mutations, or variant allele frequency between patients undergoing HCT with PB/BM blasts <5% vs those with active leukemia. Genetic factors, namely cytogenetic alterations and TP53 mutation status, rather than degree of cytoreduction predict outcomes of HCT in MPN-BP. No meaningful benefit of conventional HCT was observed in patients with MPN-BP and mutated TP53.

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Role of DYRK1A in MPN

Project description:We aim to investigate the role of DYRK1A gene in MPN pathogenesis by DYRK inhibitor and genetic knockout

2025-03-03 | GSE228060 | GEO

CPX-351 (Vyxeos™) treatment in blast-phase myeloproliferative neoplasm (MPN-BP): real-world experience in 12 consecutive cases.

Project description: Not available

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