In order to identify CLL patients for whom irradiation could be beneficial, we investigated the relationship between in vitro radio-induced apoptosis of leukemic cells and response to low-dose splenic or lymph node radiotherapy. Fourteen patients were included in the in vitro study. Leukemic cells were analyzed by Hoechst staining immediately after collection or 24h of culture following in vitro irradiation of 0-10 Gy. The tumor response rate was 47% (one CR and six PR), with a mean duration of response of 3 months (range: 1-4). A high correlation between tumor response and in vitro tests was observed (p < 0.01) and the positive predictive value of the in vitro tests for tumor and hematological responses was 100% at 5 Gy. These results suggest that the sensitivity of leukemic cells to irradiation should be first evaluated in an in vitro assay to spare refractory patients from the useless toxicity radiotherapy.
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http://dx.doi.org/10.1080/10428190290016962 | DOI Listing |
Nat Commun
January 2025
Department of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA.
ETV6::RUNX1 is the most common fusion gene in childhood acute lymphoblastic leukemia (ALL) associated with favorable prognosis, but the optimal therapy for this subtype remains unclear. Profiling the genomic and pharmacological landscape of 194 pediatric ETV6::RUNX1 ALL cases, we uncover two transcriptomic clusters, C1 (61%) and C2 (39%). Compared to C1, the C2 subtype features higher white blood cell counts and younger age at diagnosis, as well as better early treatment responses.
View Article and Find Full Text PDFFront Pharmacol
January 2025
Institute of Pharmaceutical Chemistry, Goethe University, Frankfurt, Germany.
5-Lipoxygenase (5-LO), encoded by the gene , is implicated in several pathologies. As key enzyme in leukotriene biosynthesis, 5-LO plays a central role in inflammatory diseases, but the 5-LO pathway has also been linked to development of certain hematological and solid tumor malignancies. Of note, previous studies have shown that the leukemogenic fusion protein MLL-AF4 strongly increases gene promoter activity.
View Article and Find Full Text PDFJ Exp Clin Cancer Res
January 2025
Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a second-line treatment with curative potential for leukemia patients. However, the prognosis of allo-HSCT patients with disease relapse or graft-versus-host disease (GvHD) is poor. CD4 or CD8 conventional T (Tconv) cells are critically involved in mediating anti-leukemic immune responses to prevent relapse and detrimental GvHD.
View Article and Find Full Text PDFAnal Chem
January 2025
Department of Bioengineering, University of Washington, SeattleWashington98195, United States.
Cell-to-cell heterogeneity in lipid signaling underlies variations in response and recurrence for many cancers, including leukemias. A highly parallel, miniaturized thin-layer chromatographic platform capable of assaying single cells was developed. Ultrasmall volumes (50 pL) of standard fluorescent lipids were separated with excellent repeatability, reproducibility, and limits of detection.
View Article and Find Full Text PDFSci Signal
January 2025
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
The small GTPase R-RAS2 regulates homeostatic proliferation and survival of T and B lymphocytes and, when present in high amounts, drives the development of B cell chronic lymphocytic leukemia. In normal and leukemic lymphocytes, R-RAS2 constitutively binds to antigen receptors through their immunoreceptor tyrosine-based activation motifs (ITAMs) and promotes tonic activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Here, we examined the molecular mechanisms underlying this direct interaction and its consequences for R-RAS2 activity.
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