Increased FGF-23 Levels Are Linked to Ineffective Erythropoiesis and Impaired Bone Mineralization in Myelodysplastic Syndromes

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.
[JCI Insight]
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
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Acute Alcohol Intoxication Impairs SHH‐Gli1 Signaling and Activation of Primitive Hematopoietic Precursor Cells in the Early Stage of Host Response to Bacteremia

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]
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
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Physioxia Enhances T Cell Development Ex Vivo from Human Hematopoietic Stem and Progenitor Cells

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.
[Stem Cells]
Shin, D., Huang, X., Gil, C.-H., Aljoufi, A., Ropa, J., & Broxmeyer, H. E. (n.d.). Physioxia enhances T cell development ex vivo from human hematopoietic stem and progenitor cells. STEM CELLS, n/a(n/a). https://doi.org/10.1002/stem.3259 Cite
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A Peripheral Immune Signature of Responsiveness to PD-1 Blockade in Patients with Classical Hodgkin Lymphoma

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
[Nature Medicine]
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
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Physioxia Enhances T Cell Development Ex Vivo from Human Hematopoietic Stem and Progenitor Cells

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.
[Stem Cells]
Shin, D., Huang, X., Gil, C.-H., Aljoufi, A., Ropa, J., & Broxmeyer, H. E. (n.d.). Physioxia enhances T cell development ex vivo from human hematopoietic stem and progenitor cells. STEM CELLS, n/a(n/a). https://doi.org/10.1002/stem.3259 Cite
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Collection and Processing of Mobilized Mouse Peripheral Blood at Lowered Oxygen Tension Yields Enhanced Numbers of Hematopoietic Stem Cells

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]
Aljoufi, A., Cooper, S., & Broxmeyer, H. E. (2020). Collection and Processing of Mobilized Mouse Peripheral Blood at Lowered Oxygen Tension Yields Enhanced Numbers of Hematopoietic Stem Cells. Stem Cell Reviews and Reports. https://doi.org/10.1007/s12015-020-10021-w Cite
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The Role of Mitochondrial Proteases in Leukemic Cells and Leukemic Stem Cells

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]
Mirali, S., & Schimmer, A. D. (n.d.). The role of mitochondrial proteases in leukemic cells and leukemic stem cells. STEM CELLS Translational Medicine, n/a(n/a). https://doi.org/10.1002/sctm.20-0142 Cite
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BryoLogyx Announces Cooperative Research and Development Agreement for Bryostatin-1 with National Cancer Institute

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.
[BryoLogyx, Inc.]
Press Release

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Chromatin Accessibility Landscape of Pediatric T-Lymphoblastic Leukemia and Human T-Cell Precursors

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]
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
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Prostaglandin E2 Stimulates cAMP Signaling and Re-Sensitizes Human Leukemia Cells to Glucocorticoid-Induced Cell Death

To identify glucocorticoid resistance pathways, investigators conducted a genome-wide, survival-based, shRNA screen in murine T cell acute lymphoblastic leukemia cells.
[Blood]
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
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Single UM171-Expanded Cord Blood Transplant Can Cure Severe Idiopathic Aplastic Anemia in Absence of Suitable Donors

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]
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
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Short-Term Exposure of Umbilical Cord Blood CD34+ Cells to Human Platelet Lysate and Cytokines Enhances Engraftment

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.
[Transfusion]
Rhéaume, M.-È., Rouleau, P., Tremblay, T., Paré, I., & Loubaki, L. (n.d.). Short-Term exposure of umbilical cord blood CD34+ cells to human platelet lysate and cytokines enhances engraftment. Transfusion, n/a(n/a). https://doi.org/10.1111/trf.15991 Cite
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