PI3Kδ Coordinates Transcriptional, Chromatin, and Metabolic Changes to Promote Effector CD8+ T Cells at the Expense of Central Memory

Using patient samples and a mouse model, scientists demonstrated that, upon activation, Pik3cdE1020K/+ CD8+ T cells exhibited exaggerated features of effector populations both in vitro and after viral infection that were associated with increased Fas-mediated apoptosis.
[Cell Reports]
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PHF6 and JAK3 Mutations Cooperate to Drive T-Cell Acute Lymphoblastic Leukemia Progression

The average survival time was shorter in patients with JAK/STAT and PHF6 comutation than that in other patients, suggesting a potential role of PHF6 in leukemia progression.
[Leukemia]
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TET3 Promotes AML Growth and Epigenetically Regulates Glucose Metabolism and Leukemic Stem Cell Associated Pathways

Investigators reported that the epigenetic factor, Ten-Eleven Translocation 3 (TET3) dioxygenase was overexpressed in acute myeloid leukemia (AML) patients and functionally validated human leukemic stem cells, and was required for leukemic growth by virtue of its regulation of glucose metabolism in AML cells.
[Leukemia]
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CCT245718, a Dual FLT3/Aurora a Inhibitor Overcomes D835Y-Mediated Resistance to FLT3 Inhibitors in Acute Myeloid Leukemia Cells

The ability of CCT245718 to overcome TKD-mediated resistance was evaluated in a cell line-based model of drug resistance to Fms-like tyrosine kinase 3 (FLT3) inhibitors.
[British Journal of Cancer]
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A STAT5B-CD9 Axis Determines Self-Renewal in Hematopoietic and Leukemic Stem Cells

Scientists found STAT5B to be specifically activated in HSCs and leukemic stem cells, where it induced many genes associated with quiescence and self-renewal, including the surface marker CD9.
[Blood]
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Whole-Genome Analysis of TET Dioxygenase Function in Regulatory T Cells

Investigators used whole-genome analyses to show that the transcriptional program and epigenetic features of Treg cells were attenuated in the absence of Tet2 and Tet3.
[EMBO Reports]
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Erythropoietin Promotes Abdominal Aortic Aneurysms in Mice through Angiogenesis and Inflammatory Infiltration

Researchers found that erythropoietin (EPO) promoted the formation of abdominal aortic aneurysm (AAA) in both Apoe−/− and wild type mice by enhancing angiogenesis, inflammation, collagen degradation, and apoptosis of smooth muscle cells and that EPO/EPO receptor signaling was essential for angiotensin II-induced AAA.
[Science Translational Medicine]
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The Novel STAT3 Inhibitor WZ-2-033 Causes Regression of Human Triple-Negative Breast Cancer and Gastric Cancer Xenografts

WZ-2-033 significantly inhibited the proliferation, colony survival, migration, and invasion of TNBC cells and gastric cancer cells with aberrant signal transducer and activator of transcription 3 (STAT3) activation.
[Acta Pharmacologica Sinica]
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Activated Interleukin-7 Receptor Signaling Drives B-Cell Acute Lymphoblastic Leukemia in Mice

The authors built mouse models expressing activated Il7r (aIL7R). B-cell intrinsic aIL7R mice developed spontaneous B-cell acute lymphoblastic leukemia, demonstrating sufficiency of Il7r activating mutations in leukemogenesis.
[Leukemia]
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M2 Macrophages, but Not M1 Macrophages, Support Megakaryopoiesis by Upregulating PI3K-AKT Pathway Activity

Aberrant bone marrow-M1/M2 MФ polarization, characterized by increased M1 MФs and decreased M2 MФs and accompanied by impaired megakaryopoiesis-supporting abilities, was found in patients with thrombocytopenia post-allotransplant.
[Signal Transduction and Targeted Therapy]
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Cabozantinib Promotes Erythroid Differentiation in K562 Erythroleukemia Cells through Global Changes in Gene Expression and JNK Activation

The authors reported that cabozantinib could promote differentiation in erythroid leukemia cells and found that K562 erythroid leukemia cells treated with 1 μM cabozantinib for 72 hours underwent erythroid lineage differentiation.
[Cancer Gene Therapy]
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