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Duault C, Kumar A, Taghi Khani A, et al. Activated natural killer cells predict poor clinical prognosis in high-risk B- and T-cell acute lymphoblastic leukemia. Blood. 2021;138(16):1465-1480doi: 10.1182/blood.2020009871.
Duault, C., Kumar, A., Taghi Khani, A., Lee, S. J., Yang, L., Huang, M., Hurtz, C., Manning, B., Ghoda, L., McDonald, T., Lacayo, N. J., Sakamoto, K. M., Carroll, M., Tasian, S. K., Marcucci, G., Yu, J., Caligiuri, M. A., Maecker, H. T., & Swaminathan, S. (2021). Activated natural killer cells predict poor clinical prognosis in high-risk B- and T-cell acute lymphoblastic leukemia. Blood, 138(16), 1465-1480. https://doi.org/10.1182/blood.2020009871
Duault, Caroline, et al. "Activated natural killer cells predict poor clinical prognosis in high-risk B- and T-cell acute lymphoblastic leukemia." Blood vol. 138,16 (2021): 1465-1480. doi: https://doi.org/10.1182/blood.2020009871
Duault C, Kumar A, Taghi Khani A, Lee SJ, Yang L, Huang M, Hurtz C, Manning B, Ghoda L, McDonald T, Lacayo NJ, Sakamoto KM, Carroll M, Tasian SK, Marcucci G, Yu J, Caligiuri MA, Maecker HT, Swaminathan S. Activated natural killer cells predict poor clinical prognosis in high-risk B- and T-cell acute lymphoblastic leukemia. Blood. 2021 Oct 21;138(16):1465-1480. doi: 10.1182/blood.2020009871. PMID: 34077953; PMCID: PMC8532198.
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Blood. 2021 Oct 21;138(16):1465-1480. doi: 10.1182/blood.2020009871.

Activated natural killer cells predict poor clinical prognosis in high-risk B- and T-cell acute lymphoblastic leukemia.

Blood

Caroline Duault, Anil Kumar, Adeleh Taghi Khani, Sung June Lee, Lu Yang, Min Huang, Christian Hurtz, Bryan Manning, Lucy Ghoda, Tinisha McDonald, Norman J Lacayo, Kathleen M Sakamoto, Martin Carroll, Sarah K Tasian, Guido Marcucci, Jianhua Yu, Michael A Caligiuri, Holden T Maecker, Srividya Swaminathan

Affiliations

  1. The Human Immune Monitoring Center, Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA.
  2. Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA.
  3. Division of Hematology/Oncology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA.
  4. Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
  5. Department of Hematological Malignancies and Translational Science, Beckman Research Institute of City of Hope, Duarte, CA.
  6. Division of Oncology and Center for Childhood Cancer Research, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA; and.
  7. Department of Hematology and Hematopoietic Stem Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA.

PMID: 34077953 PMCID: PMC8532198 DOI: 10.1182/blood.2020009871

Abstract

B- and T-cell acute lymphoblastic leukemia (B/T-ALL) may be refractory or recur after therapy by suppressing host anticancer immune surveillance mediated specifically by natural killer (NK) cells. We delineated the phenotypic and functional defects in NK cells from high-risk patients with B/T-ALL using mass cytometry, flow cytometry, and in silico cytometry, with the goal of further elucidating the role of NK cells in sustaining acute lymphoblastic leukemia (ALL) regression. We found that, compared with their normal counterparts, NK cells from patients with B/T-ALL are less cytotoxic but exhibit an activated signature that is characterized by high CD56, high CD69, production of activated NK cell-origin cytokines, and calcium (Ca2+) signaling. We demonstrated that defective maturation of NK cells into cytotoxic effectors prevents NK cells from ALL from lysing NK cell-sensitive targets as efficiently as do normal NK cells. Additionally, we showed that NK cells in ALL are exhausted, which is likely caused by their chronic activation. We found that increased frequencies of activated cytokine-producing NK cells are associated with increased disease severity and independently predict poor clinical outcome in patients with ALL. Our studies highlight the benefits of developing NK cell profiling as a diagnostic tool to predict clinical outcome in patients with ALL and underscore the clinical potential of allogeneic NK cell infusions to prevent ALL recurrence.

© 2021 by The American Society of Hematology.

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