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Defining 2 Biologically and Clinically Distinct Groups in Acute Leukemia with a Mixed Phenotype.
Blood
January 2025
Memorial Sloan Kettering Cancer Center, New York, New York, United States.
A mixed phenotype is characteristic of de novo Mixed Phenotype Acute Leukemia (MPAL) but can also be seen in other leukemias. It poses substantial classification and management dilemmas. Herein, we report a large cohort of acute leukemia with a mixed phenotype and define Acute Myeloid Leukemia with Mixed Phenotype (AML-MP) and MPAL as two distinct groups by characterizing the clinical, genetic, and transcriptomic features.
View Article and Find Full Text PDFGenomic and phenotypic stability of fusion-driven pediatric sarcoma cell lines.
Nat Commun
January 2025
Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.
Human cancer cell lines are the mainstay of cancer research. Recent reports showed that highly mutated adult carcinoma cell lines (mainly HeLa and MCF-7) present striking diversity across laboratories and that long-term continuous culturing results in genomic/transcriptomic heterogeneity with strong phenotypical implications. Here, we hypothesize that oligomutated pediatric sarcoma cell lines mainly driven by a fusion transcription factor, such as Ewing sarcoma (EwS), are genetically and phenotypically more stable than the previously investigated adult carcinoma cell lines.
View Article and Find Full Text PDFRNA-binding proteins hnRNPM and ELAVL1 promote type-I interferon induction downstream of the nucleic acid sensors cGAS and RIG-I.
EMBO J
December 2024
Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany.
The cytosolic nucleic acid sensors RIG-I and cGAS induce type-I interferon (IFN)-mediated immune responses to RNA and DNA viruses, respectively. So far no connection between the two cytosolic pathways upstream of IKK-like kinase activation has been investigated. Here, we identify heterogeneous nuclear ribonucleoprotein M (hnRNPM) as a positive regulator of IRF3 phosphorylation and type-I IFN induction downstream of both cGAS and RIG-I.
View Article and Find Full Text PDFA TRAILR2/CDH3 bispecific antibody demonstrates selective apoptosis and tumor regression in CDH3-positive pancreatic cancer.
MAbs
December 2024
Cancer Research Therapeutic Area, Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria.
Article Synopsis
- Exploiting TRAILR2 activation could improve cancer treatments, but past therapies faced issues like low effectiveness and liver damage.
- The new TR2/CDH3 BAB antibody targets both CDH3 and TRAILR2, enhancing apoptosis specifically in tumor cells expressing CDH3, showcasing effectiveness in various cancers and CRISPR-engineered models.
- In pancreatic cancer, where current treatments are lacking, TR2/CDH3 BAB shows promise, especially when used with other chemotherapy drugs, indicating potential for effective cancer therapy with a good safety profile.
Single-cell multiomics reveal divergent effects of DNMT3A- and TET2-mutant clonal hematopoiesis in inflammatory response.
Blood Adv
January 2025
Department of Laboratory Medicine and Pathology, Epigenomics Program, Center for Individualized Medicine, Mayo Clinic, Rochester, MN.
DNMT3A and TET2 are epigenetic regulator genes commonly mutated in age-related clonal hematopoiesis (CH). Despite having opposed epigenetic functions, these mutations are associated with increased all-cause mortality and a low risk for progression to hematologic neoplasms. Although individual impacts on the epigenome have been described using different model systems, the phenotypic complexity in humans remains to be elucidated.
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