Functional Reconstruction of Human AML Reveals Stem Cell Origin and Vulnerability of Treatment-Resistant MLL-Rearranged Leukemia

HSC-derived Mixed Lineage Leukemia- acute myeloid leukemia gene fusions was highly resistant to chemotherapy and expressed elevated amounts of the multispecific anion transporter ABCC3.
[Science Translational Medicine]
Zeisig, B. B., Fung, T. K., Zarowiecki, M., Tsai, C. T., Luo, H., Stanojevic, B., Lynn, C., Leung, A. Y. H., Zuna, J., Zaliova, M., Bornhauser, M., Bonin, M. von, Lenhard, B., Huang, S., Mufti, G. J., & So, C. W. E. (2021). Functional reconstruction of human AML reveals stem cell origin and vulnerability of treatment-resistant MLL-rearranged leukemia. Science Translational Medicine, 13(582). https://doi.org/10.1126/scitranslmed.abc4822 Cite
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Flow Cytometric Immunophenotypic Alterations of Persistent Clonal Haematopoiesis in Remission Bone Marrows of Patients with NPM1-Mutated Acute Myeloid Leukemia

From a consecutive cohort of 67 patients with nucleophosmin 1‐mutated (NPM1mut) acute myeloid leukemia , investigators identified 50 who achieved NPM1mut clearance and had parallel multicolour flow cytometry and next generation sequencing.
[British Journal of Haematology]
Loghavi, S., DiNardo, C. D., Furudate, K., Takahashi, K., Tanaka, T., Short, N. J., Kadia, T., Konopleva, M., Kanagal‐Shamanna, R., Farnoud, N. R., Pierce, S., Khoury, J. D., Jorgensen, J. L., Patel, K. P., Daver, N., Yilmaz, M., Medeiros, L. J., Kantarjian, H., Ravandi, F., & Wang, S. A. (n.d.). Flow cytometric immunophenotypic alterations of persistent clonal haematopoiesis in remission bone marrows of patients with NPM1-mutated acute myeloid leukaemia. British Journal of Haematology, n/a(n/a). https://doi.org/https://doi.org/10.1111/bjh.17347 Cite
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CD20 as a Gatekeeper of the Resting State of Human B Cells

Researchers demonstrated that CD20 controlled the nanoscale organization of receptors on the surface of resting B lymphocytes.
[Proceedings of the National Academy of Sciences of the United States of America]
Kläsener, K., Jellusova, J., Andrieux, G., Salzer, U., Böhler, C., Steiner, S. N., Albinus, J. B., Cavallari, M., Süß, B., Voll, R. E., Boerries, M., Wollscheid, B., & Reth, M. (2021). CD20 as a gatekeeper of the resting state of human B cells. Proceedings of the National Academy of Sciences, 118(7). https://doi.org/10.1073/pnas.2021342118 Cite
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Targeting Tumor-Associated Macrophages to Synergize Tumor Immunotherapy

Scientists summarize recent studies investigating the involvement of TAMs in immune checkpoint inhibition, tumor vaccines and adoptive cell transfer therapies.
[Signal Transduction and Targeted Therapy]
Xiang, X., Wang, J., Lu, D., & Xu, X. (2021). Targeting tumor-associated macrophages to synergize tumor immunotherapy. Signal Transduction and Targeted Therapy, 6(1), 1–12. https://doi.org/10.1038/s41392-021-00484-9 Cite
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Hematopoietic Stem Cell Heterogeneity Is Linked to the Initiation and Therapeutic Response of Myeloproliferative Neoplasms

Single-cell gene expression profiling with parallel mutation detection demonstrated that the megakaryocyte-primed hematopoietic stem cells subpopulation expanded significantly with enhanced potential in untreated individuals with JAK2V617F+essential thrombocythemia, driven primarily by the JAK2 mutation and elevated interferon signaling.
[Cell Stem Cell]
Tong, J., Sun, T., Ma, S., Zhao, Y., Ju, M., Gao, Y., Zhu, P., Tan, P., Fu, R., Zhang, A., Wang, D., Wang, D., Xiao, Z., Zhou, J., Yang, R., Loughran, S. J., Li, J., Green, A. R., Bresnick, E. H., … Shi, L. (2021). Hematopoietic Stem Cell Heterogeneity Is Linked to the Initiation and Therapeutic Response of Myeloproliferative Neoplasms. Cell Stem Cell, 0(0). https://doi.org/10.1016/j.stem.2021.01.018 Cite
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Facilitative Lysosomal Transport of Bile Acids Alleviates ER Stress in Mouse Hematopoietic Precursors

Scientists demonstrated that lysosomal equilibrative nucleoside transporter 3 (ENT3) transport of taurine-conjugated bile acids (TBA) facilitated TBA chemical chaperone function and alleviated endoplasmic reticulum stress in expanding mouse hematopoietic stem and progenitor cells.
[Nature Communications]
Persaud, A. K., Nair, S., Rahman, M. F., Raj, R., Weadick, B., Nayak, D., McElroy, C., Shanmugam, M., Knoblaugh, S., Cheng, X., & Govindarajan, R. (2021). Facilitative lysosomal transport of bile acids alleviates ER stress in mouse hematopoietic precursors. Nature Communications, 12(1), 1248. https://doi.org/10.1038/s41467-021-21451-6 Cite
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Acute Leukemia in Infants

International collaborative clinical trials have led to better understanding of the underlying molecular biology, refined risk-based stratification, and investigated the use of hematopoietic stem cell transplantation.
[Current Oncology Reports]
Ibrahimova, A., Pommert, L., & Breese, E. H. (2021). Acute Leukemia in Infants. Current Oncology Reports, 23(3), 27. https://doi.org/10.1007/s11912-021-01021-1 Cite
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Immunotherapies Old and New: Hematopoietic Stem Cell Transplant, Chimeric Antigen Receptor T Cells, and Bispecific Antibodies for the Treatment of Relapsed/Refractory Diffuse Large B Cell Lymphoma

The authors discuss their approach to relapsed or refractory diffuse large B cell lymphoma patients and the open question of optimal sequencing of autologous transplant , CAR-T therapy, and bispecific antibodies.
[Current Hematologic Malignancy Reports]
Doraiswamy, A., Shah, M. R., & Bannerji, R. (2021). Immunotherapies Old and New: Hematopoietic Stem Cell Transplant, Chimeric Antigen Receptor T Cells, and Bispecific Antibodies for the Treatment of Relapsed/Refractory Diffuse Large B Cell Lymphoma. Current Hematologic Malignancy Reports. https://doi.org/10.1007/s11899-021-00610-y Cite
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A Molecular Biologist Has Been Awarded Funding to Support a New Method of Research into Blood Cancer

Dr. Salvatore Papa, an Assistant Professor in Cancer Research at the University of Leeds, has been awarded Leukaemia & Myeloma Research UK’s research grant to continue his specialist studies into examining how the accumulation of mutated proteins in certain blood cancer cells allows them to multiply repeatedly.
[Charity Today]
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Recent FDA Designation Puts Promising Engineered Cellular Therapy that Reduces Complications of Lymphoma Treatment on Accelerated Path to Market Approval

In November 2020, the FDA granted Regenerative Medicine Advanced Therapy designation for a cellular therapy called AB-205. AB-205 acts promptly to repair injured vascular niches of organs to prevent or reduce severe toxicities in patients who have Hodgkin lymphoma or non-Hodgkin lymphoma undergoing high dose chemotherapy and autologous stem cell transplantation.
[Hackensack University Medical Center (Newswise, Inc.)]
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EKLF/KLF1 Expression Defines a Unique Macrophage Subset during Mouse Erythropoiesis

Using unbiased global sequencing and directed genetic approaches focused on early mammalian development, the authors found that fetal liver macrophage exhibit a unique expression signature that differentiates them from erythroid and adult macrophage cells.
[eLife]
Mukherjee, K., Xue, L., Planutis, A., Gnanapragasam, M. N., Chess, A., & Bieker, J. J. (2021). EKLF/KLF1 expression defines a unique macrophage subset during mouse erythropoiesis. ELife, 10, e61070. https://doi.org/10.7554/eLife.61070 Cite
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