A butylnitrosourea-induced murine T-cell leukemia, L40, was transplanted in BDF1 mice; 1 X 10(3) cells killed all recipients after conditioning with 400 rad, whereas 1 X 10(5) were needed with normal recipients. No leukemic cells could be detected by transplantation or cytogenetic analysis in the femur or the spleen at day 6 after L40 inoculation and, at day 11, leukemic cells were found in one out of two experiments, more if the host had been irradiated. Up to day 17, when leukemic cells were present, the CFU-S and CFU-C content of the femur was normal, but later a loss was observed with an increase in the enlarging spleen. Lymphocyte-stimulation assays with spleen cells gave normal results up to day 17, but later the 3H-thymidine uptake of stimulated T and B cells was reduced. The NK-cell activity with and without stimulation by Corynebacterium parvum in the spleen began to fall at day 17 and was absent later; this loss was also observed with peritoneal exudate cells. In vitro mixing experiments of L40 cells with normal spleen cells showed "cold target inhibition" by L40 cells in the NK-cell assay as well as interference with the lymphocyte stimulation.
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Acta Pharmacol Sin
January 2025
School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.
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Division of Pediatric Hematology/Oncology, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, United States of America.
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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.
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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.
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Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
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