Cancer Therapy Shapes the Fitness Landscape of Clonal Hematopoiesis

Understanding of the processes that drive transformation of certain clones to cancer is limited. Researchers study this phenomenon in the context of clonal hematopoiesis and the development of therapy-related myeloid neoplasms.
[Nature Genetics]
Bolton, K. L., Ptashkin, R. N., Gao, T., Braunstein, L., Devlin, S. M., Kelly, D., Patel, M., Berthon, A., Syed, A., Yabe, M., Coombs, C. C., Caltabellotta, N. M., Walsh, M., Offit, K., Stadler, Z., Mandelker, D., Schulman, J., Patel, A., Philip, J., … Papaemmanuil, E. (2020). Cancer therapy shapes the fitness landscape of clonal hematopoiesis. Nature Genetics, 1–8. https://doi.org/10.1038/s41588-020-00710-0 Cite
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Keros Therapeutics, Inc. Announces Dosing of First Participants in Phase II Clinical Trial of KER-050 in Myelodysplastic Syndromes (MDS)

Keros Therapeutics, Inc. announced that it has dosed the first two participants in a Phase II clinical trial evaluating KER-050 for the treatment of anemia and thrombocytopenia in myelodysplastic syndromes.
[Keros Therapeutics, Inc.]
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Transcriptional Profile of Platelets and iPSC-Derived Megakaryocytes from Whole Genome and RNA Sequencing

In 290 normal subjects from the GeneSTAR Research Study, investigators generated whole genome sequence data from whole blood and RNA sequence data from extracted non-ribosomal RNA from 185 induced pluripotent stem cell-derived megakaryocyte cell lines and 290 blood platelet samples from these subjects.
[Blood]
Kammers, K., Taub, M., Rodriguez, B., Yanek, L. R., Ruczinski, I., Martin, J., Kanchan, K., Battle, A., Cheng, L., Wang, Z. Z., Johnson, A. D., Leek, J., Faraday, N., Becker, L., & Mathias, R. (n.d.). Transcriptional profile of platelets and iPSC-derived megakaryocytes from whole genome and RNA sequencing. Blood. https://doi.org/10.1182/blood.2020006115 Cite
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A Trispecific Killer Engager Molecule Against CLEC12A Effectively Induces NK-Cell Mediated Killing of AML Cells

To target acute myeloid leukemia blasts and leukemic stem cells using natural killer (NK) cells, scientists developed a trispecific killer engager molecule containing a humanized anti-CD16 heavy chain camelid single-domain antibody that activates NK cells.
[Leukemia]
Arvindam, U. S., van Hauten, P. M. M., Schirm, D., Schaap, N., Hobo, W., Blazar, B. R., Vallera, D. A., Dolstra, H., Felices, M., & Miller, J. S. (2020). A trispecific killer engager molecule against CLEC12A effectively induces NK-cell mediated killing of AML cells. Leukemia, 1–11. https://doi.org/10.1038/s41375-020-01065-5 Cite
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Antileukemic Activity of the VPS34-IN1 Inhibitor in Acute Myeloid Leukemia

Using a recently developed specific inhibitor, the authors found that vacuolar protein sorting 34 inhibition induces apoptosis in acute myeloid leukemia cells but not in normal CD34+ hematopoietic cells.
[Oncogenesis]
Meunier, G., Birsen, R., Cazelles, C., Belhadj, M., Cantero-Aguilar, L., Kosmider, O., Fontenay, M., Azar, N., Mayeux, P., Chapuis, N., Tamburini, J., & Bouscary, D. (2020). Antileukemic activity of the VPS34-IN1 inhibitor in acute myeloid leukemia. Oncogenesis, 9(10), 1–14. https://doi.org/10.1038/s41389-020-00278-8 Cite
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Epigenetic Regulators as the Gatekeepers of Hematopoiesis

Researchers bring together what is currently known about chromatin status and the development of cells in the hematopoietic system under normal and abnormal conditions.
[Trends in Genetics]
Rodrigues, C. P., Shvedunova, M., & Akhtar, A. (2020). Epigenetic Regulators as the Gatekeepers of Hematopoiesis. Trends in Genetics, 0(0). https://doi.org/10.1016/j.tig.2020.09.015 Cite
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Human Hematopoietic Stem, Progenitor, and Immune Cells Respond Ex Vivo to SARS-CoV-2 Spike Protein

Scientists examined the expression of ACE2, to which SARS-CoV-2 Spike protein binds to facilitate viral entry, in cord blood derived hematopoietic stem cells/hematopoietic progenitor cells and in peripheral blood derived immune cell subtypes.
[Stem Cell Reviews and Reports]
Ropa, J., Cooper, S., Capitano, M. L., Van’t Hof, W., & Broxmeyer, H. E. (2020). Human Hematopoietic Stem, Progenitor, and Immune Cells Respond Ex Vivo to SARS-CoV-2 Spike Protein. Stem Cell Reviews and Reports. https://doi.org/10.1007/s12015-020-10056-z Cite
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Microtubules Control Nuclear Shape and Gene Expression during Early Stages of Hematopoietic Differentiation

Researchers showed that large invaginations were generated by microtubule constraints on the swelling nucleus of human hematopoietic stem and progenitor cells during early commitment toward the myeloid lineage.
[EMBO Journal]
Biedzinski, S., Agsu, G., Vianay, B., Delord, M., Blanchoin, L., Larghero, J., Faivre, L., Théry, M., & Brunet, S. (2020). Microtubules control nuclear shape and gene expression during early stages of hematopoietic differentiation. The EMBO Journal, n/a(n/a), e103957. https://doi.org/10.15252/embj.2019103957 Cite
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HTLV-1 Targets Human Placental Trophoblasts in Seropositive Pregnant Women

Investigators found that human T cell leukemia virus type 1 proviral DNA was present in the placental villous tissues of the fetuses of nearly half of pregnant carriers and in a small number of cord blood samples.
[Journal of Clinical Investigation]
Tezuka, K., Fuchi, N., Okuma, K., Tsukiyama, T., Miura, S., Hasegawa, Y., Nagata, A., Komatsu, N., Hasegawa, H., Sasaki, D., Sasaki, E., Mizukami, T., Kuramitsu, M., Matsuoka, S., Yanagihara, K., Miura, K., & Hamaguchi, I. (2020). HTLV-1 targets human placental trophoblasts in seropositive pregnant women. The Journal of Clinical Investigation, 130(11). https://doi.org/10.1172/JCI135525 Cite
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Mitochondrial Potentiation Ameliorates Age-Related Heterogeneity in Hematopoietic Stem Cell Function

Researchers showed that mitochondrial membrane potential can be used to prospectively isolate chronologically old hematopoietic stem cells (HSCs) with transcriptional features and functional attributes characteristic of young HSCs, including a high rate of transcription and balanced lineage-affiliated programs.
[Cell Stem Cell]
Mansell, E., Sigurdsson, V., Deltcheva, E., Brown, J., James, C., Miharada, K., Soneji, S., Larsson, J., & Enver, T. (2020). Mitochondrial Potentiation Ameliorates Age-Related Heterogeneity in Hematopoietic Stem Cell Function. Cell Stem Cell, 0(0). https://doi.org/10.1016/j.stem.2020.09.018 Cite
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Agios Announces Withdrawal of European Marketing Authorization Application for TIBSOVO® as a Treatment for Relapsed or Refractory IDH1-mutant Acute Myeloid Leukemia

Agios Pharmaceuticals, Inc. announced the withdrawal of its European Marketing Authorization Application for TIBSOVO® for the treatment of adult patients with relapsed or refractory acute myeloid leukemia with an isocitrate dehydrogenase-1 mutation.
[Agios Pharmaceuticals, Inc]
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