Researchers showed that myelodysplastic NUP98‑HOXD13 transgenic mice displayed an abnormally high number of osteoblasts, yet a higher fraction of nonmineralized bone, indicating delayed bone mineralization. This was accompanied by high fibroblast growth factor-23 serum levels, a phosphaturic hormone that inhibits bone mineralization and erythropoiesis.
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Weidner, H., Baschant, U., Lademann, F., Colunga, M. G. L., Balaian, E., Hofbauer, C., Misof, B. M., Roschger, P., Blouin, S., Richards, W. G., Platzbecker, U., Hofbauer, L. C., & Rauner, M. (2020). Increased FGF-23 levels are linked to ineffective erythropoiesis and impaired bone mineralization in myelodysplastic syndromes. JCI Insight, 5(15). https://doi.org/10.1172/jci.insight.137062 Cite
Investigators determined the effect of alcohol exposure on sonic hedgehog signaling in the regulation of hematopoietic stem cell activation during bacteremia.
[Alcoholism-Clinical and Experimental Research]
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Shi, X., Simms, K. J., & Zhang, P. (n.d.). Acute Alcohol Intoxication Impairs SHH-Gli1 Signaling and Activation of Primitive Hematopoietic Precursor Cells in the Early Stage of Host Response to Bacteremia. Alcoholism: Clinical and Experimental Research, n/a(n/a). https://doi.org/10.1111/acer.14429 Cite
Investigators report that physiologically relevant oxygen concentration, an important environmental thymic factor promotes differentiation of cord blood CD34+ cells into progenitor T cells in serum‐free and feeder‐free culture system.
Investigators utilized the complementary approaches of T cell receptor sequencing and cytometry by time-of-flight analysis to obtain a peripheral immune signature of responsiveness to PD-1 blockade in 56 patients treated in the CheckMate 205 Phase II clinical trial
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Cader, F. Z., Hu, X., Goh, W. L., Wienand, K., Ouyang, J., Mandato, E., Redd, R., Lawton, L. N., Chen, P.-H., Weirather, J. L., Schackmann, R. C. J., Li, B., Ma, W., Armand, P., Rodig, S. J., Neuberg, D., Liu, X. S., & Shipp, M. A. (2020). A peripheral immune signature of responsiveness to PD-1 blockade in patients with classical Hodgkin lymphoma. Nature Medicine, 1–12. https://doi.org/10.1038/s41591-020-1006-1 Cite
Scientists report that physiologically relevant oxygen concentration, an important environmental thymic factor promotes differentiation of cord blood CD34+ cells into progenitor T cells in serum‐free and feeder‐free culture system. This effect was enhanced by a potent reducing and antioxidant agent, ascorbic acid.
The authors demonstrated that similar to mouse bone marrow and human cord blood, collection and processing of mouse Granulocyte Colony Stimulating Factor (G-CSF)-, AMD3100/Plerixafor- or G-CSF plus AMD3100/Plerixafor-mobilized HSCs in 3% O2 resulted in enhanced numbers of rigorously-defined phenotypic and for G-CSF – and G-CSF plus AMD3100/Plerixafor – mPB enhanced functionally-engrafting hematopoietic stem cells.
[Stem Cell Reviews and Reports]
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Investigators highlight the functional consequences of inhibiting and activating mitochondrial proteases and discuss their potential as therapeutic targets in acute myeloid leukemia.
[Stem Cells Translational Medicine]
BryoLogyx, Inc. announced that it has entered into a Cooperative Research and Development Agreement with the National Cancer Institute, to conduct a Phase I clinical trial with bryostatin-1 in pediatric and young adult patients with relapsing or refractory CD22 expressing acute lymphoblastic leukemia and lymphoma.
Developmental stages were distinguished by 2,823 signature chromatin regions with 95% accuracy. Open chromatin surrounding SAE 1 was identified to best distinguish thymic developmental stages suggesting a potential role of SUMO ylation in T‐cell development.
[EMBO Molecular Medicine]
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Erarslan-Uysal, B., Kunz, J. B., Rausch, T., Richter-Pechańska, P., van Belzen, I. A., Frismantas, V., Bornhauser, B., Ordoñez-Rueada, D., Paulsen, M., Benes, V., Stanulla, M., Schrappe, M., Cario, G., Escherich, G., Bakharevich, K., Kirschner-Schwabe, R., Eckert, C., Loukanov, T., Gorenflo, M., … Kulozik, A. E. (2020). Chromatin accessibility landscape of pediatric T-lymphoblastic leukemia and human T-cell precursors. EMBO Molecular Medicine, n/a(n/a), e12104. https://doi.org/10.15252/emmm.202012104 Cite
To identify glucocorticoid resistance pathways, investigators conducted a genome-wide, survival-based, shRNA screen in murine T cell acute lymphoblastic leukemia cells.
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Roderick, J. E., Gallagher, K. M., Murphy, L. C., O’Connor, K. W., Tang, K., Zhang, B., Brehm, M., Greiner, D. L., Yu, J., Zhu, L. J., Green, M. R., & Kelliher, M. A. (n.d.). Prostaglandin E2 stimulates cAMP signaling and re-sensitizes human leukemia cells to glucocorticoid-induced cell death. Blood. https://doi.org/10.1182/blood.2020005712 Cite
Investigators report the first case of an adult patient with severe aplastic anemia who was successfully transplanted with a UM171‐expanded cord blood graft. After a conditioning of rabbit anti‐thymocyte globulin, fludarabine, cyclophosphamide and total body irradiation, a UM171 expanded graft of 3.29 x 106 CD34+ cells/kg was infused.
[European Journal of Haematology]
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Claveau, J.-S., Cohen, S., Ahmad, I., Delisle, J.-S., Kiss, T., Lachance, S., Sauvageau, G., Busque, L., Brito, R.-M., Bambace, N., Bernard, L., Roy, D. C., & Roy, J. (n.d.). Single UM171-expanded cord blood transplant can cure severe idiopathic aplastic anemia in absence of suitable donors. European Journal of Haematology, n/a(n/a). https://doi.org/10.1111/ejh.13504 Cite
Hematopoietic progenitor stem cells (HSPCs) were isolated from human umbilical cord blood. HSPC were seeded in the wells of a 24‐well microplate and exposed to increasing concentrations of human platelet lysates with or without cytokines for 24 hours.