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Childhood leukaemia in Down's syndrome primed by blood-cell biasAn in-depth investigation of gene regulation and cell populations at sites of fetal blood-cell production provides clues as to why children with Down’s syndrome are predisposed to developing leukaemia.
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Efficacy of DYRK1A inhibitors in novel models of Down syndrome acute lymphoblastic leukemiaDespite significant advances, outcomes for children with Down syndrome (DS, trisomy 21) who develop acute lymphoblastic leukemia remain poor. Reports of large DS-ALL cohorts have shown that children with DS have inferior event-free survival and overall survival compared to children without DS.
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SNAIL trail in myeloid malignanciesTranscription factors known to induce the epithelial-to-mesenchymal transition (EMT) (such as ZEB1/2 [zinc finger E-box binding homeobox 1/2], SNAI1/2/3, and TWIST1/2) have been undoubtedly implicated in tumorigenesis, cancer progression, metastasis, and chemoresistance in solid tumors; however, their role in normal and malignant hematopoiesis has been underappreciated for many years.
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DYRK1A regulates B cell acute lymphoblastic leukemia through phosphorylation of FOXO1 and STAT3DYRK1A is a serine/threonine kinase encoded on human chromosome 21 (HSA21) that has been implicated in several pathologies of Down syndrome (DS), including cognitive deficits and Alzheimer's disease. Although children with DS are predisposed to developing leukemia, especially B cell acute lymphoblastic leukemia (B-ALL), the HSA21 genes that contribute to malignancies remain largely undefined. Here, we report that DYRK1A is overexpressed and required for B-ALL. Genetic and pharmacologic inhibition of DYRK1A decreased leukemic cell expansion and suppressed B-ALL development in vitro and in vivo.
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Romidepsin enhances the efficacy of cytarabine in vivo, revealing HDAC inhibition as a therapeutic strategy for KMT2A-rearranged acute lymphoblastic leukemiaIn this study, we investigate the in vivo synergy between romidepsin and cytarabine
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Partial trisomy 21 contributes to T-cell malignancies induced by JAK3-activating mutations in murine modelsThis JAK3A572V knockin model is a relevant new tool for testing the efficacy of JAK inhibitors in JAK3-related hematopoietic malignancies
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Characterization of mesenchymal stem cells in pre-B acute lymphoblastic leukemiaComponents of the bone marrow microenvironment (BMM) have been shown to mediate the way in which leukemia develops, progresses and responds to treatment. Increasing evidence shows that leukemic cells hijack the BMM, altering its functioning and establishing leukemia-supportive interactions with stromal and immune cells.
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Tracking of activated cTfh cells following sequential influenza vaccinations reveals transcriptional profile of clonotypes driving a vaccine-induced immune responseA vaccine against influenza is available seasonally but is not 100% effective. A predictor of successful seroconversion in adults is an increase in activated circulating T follicular helper (cTfh) cells after vaccination. However, the impact of repeated annual vaccinations on long-term protection and seasonal vaccine efficacy remains unclear.
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A CHAF1B-Dependent Molecular Switch in Hematopoiesis and Leukemia PathogenesisHere we report that CHAF1B is required for normal hematopoiesis while its overexpression promotes leukemia