The authors identified the efficacy of ruxolitinib in human leukocyte antigen haploidentical hematopoietic stem cell transplantation recipients with multidrug-resistant-graft-versus-host disease.
[Annals of Hematology]
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Zhao, J.-Y., Liu, S.-N., Xu, L.-P., Zhang, X.-H., Wang, Y., Chen, Y.-H., Liu, K.-Y., Huang, X.-J., & Mo, X.-D. (2020). Ruxolitinib is an effective salvage treatment for multidrug-resistant graft-versus-host disease after haploidentical allogeneic hematopoietic stem cell transplantation without posttransplant cyclophosphamide. Annals of Hematology. https://doi.org/10.1007/s00277-020-04273-2 Cite
Considering the most important signaling pathways involved in the self-renewal of hematopoietic stem cells, CB-CD34+ cells were expanded with cytokines in the presence of seven small molecules including SB, PD, Chir, Bpv, Pur, Pμ, and NAM.
[Stem Cell Research & Therapy]
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Using in vitro and in vivo experimental approaches, researchers demonstrated that leptin receptor (Lepr) differentiates SLAM hematopoietic stem cells (HSCs) into two distinct populations; Lepr+ HSCs engrafted better than Lepr− HSCs in primary transplant.
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Rig-I or Mda5 deficiency reduced hematopoietic stem and progenitor cell numbers by inhibiting inflammatory signals that were in turn enhanced in Lgp2 deficient embryos.
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Lefkopoulos, S., Polyzou, A., Derecka, M., Bergo, V., Clapes, T., Cauchy, P., Jerez-Longres, C., Onishi-Seebacher, M., Yin, N., Martagon-Calderón, N.-A., Potts, K. S., Klaeylé, L., Liu, F., Bowman, T. V., Jenuwein, T., Mione, M. C., & Trompouki, E. (2020). Repetitive Elements Trigger RIG-I-like Receptor Signaling that Regulates the Emergence of Hematopoietic Stem and Progenitor Cells. Immunity, 0(0). https://doi.org/10.1016/j.immuni.2020.10.007 Cite
The authors focus on new findings that clarify the roles specific epigenetic regulators play in T cell-mediated aGVHD development and discusses how their modulation could disrupt that process to beneficial effects.
The authors used single-cell RNA sequencing to characterize the kinetics of the murine bone marrow microenvironment during B cell acute lymphoblastic leukemia progression. Normal pro- and pre-B cells were found to be the most affected at the earliest stages of disease and this was associated with changes in expression of genes regulated by the AP1-transcription factor complex and regulatory factors NELFE, MYC and BCL11A.
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Anderson, D., Skut, P., Hughes, A. M., Ferrari, E., Tickner, J., Xu, J., Mullin, B. H., Tang, D., Malinge, S., Kees, U. R., Kotecha, R. S., Lassmann, T., & Cheung, L. C. (2020). The bone marrow microenvironment of pre-B acute lymphoblastic leukemia at single-cell resolution. Scientific Reports, 10(1), 19173. https://doi.org/10.1038/s41598-020-76157-4 Cite
Hydrogen sulfide increases the expression of CXCR4 on HSPCs, enhancing their migration towards SDF-1α in-vitro and thus homing to bone marrow niche along with the higher capacity to repopulate.
[Cell Adhesion & Migration]
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Investigators retrospectively compared the efficacy and safety of preemptive recombinant interleukin-2 and pre-DLI for late-onset minimal residual disease in patients receiving allogeneic hematopoietic stem cell transplantation for acute leukemia or myelodysplastic syndrome.
[Annals of Hematology]
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The IL1β-induced inflammatory secretome of IL1RAPexpressing acute myeloid leukemia (AML) cells grown on a stromal layer of MSCs affected normal hematopoiesis including hematopoietic stem/progenitor cells while AML cell proliferation was not affected.
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Boer, B. de, Sheveleva, S., Apelt, K., Vellenga, E., Mulder, A. B., Schuringa, G. H., & Jacob, J. (2020). The IL1-IL1RAP axis plays an important role in the inflammatory leukemic niche that favors acute myeloid leukemia proliferation over normal hematopoiesis. Haematologica, 0–0. https://doi.org/10.3324/haematol.2020.254987 Cite
Investigators analyzed peripheral-blood exome sequence data independent of clinical phenotype and inheritance pattern to identify deleterious mutations in ubiquitin-related genes.
[New England Journal of Medicine]
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Beck, D. B., Ferrada, M. A., Sikora, K. A., Ombrello, A. K., Collins, J. C., Pei, W., Balanda, N., Ross, D. L., Cardona, D. O., Wu, Z., Patel, B., Manthiram, K., Groarke, E. M., Gutierrez-Rodrigues, F., Hoffmann, P., Rosenzweig, S., Nakabo, S., Dillon, L. W., Hourigan, C. S., … Grayson, P. C. (2020). Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease. New England Journal of Medicine. https://doi.org/10.1056/NEJMoa2026834 Cite
Scientists demonstrated that, unlike Bacille Calmette-Guérin or β-glucan, Mycobacterium tuberculosis (Mtb) reprograms HSCs via an IFN-I response that suppresses myelopoiesis and impairs development of protective trained immunity to Mtb.
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