Evaluation of Serum Interleukin-15 in Acute Lymphoid and Myeloid Leukemia Patients

Document Type : Original Articles

Author

College of Biotechnology, University of Al-Qadisiyah, Al Diwaniyah, Iraq

Abstract

The interleukin-15 is a unique proinflammatory cytokine associated with immune response regulation and the growth, survival, and biological behavior of leukemic cells. This study assesses the effect of both types of acute malignancies, lymphoid and myeloid, on the interleukin-15 serum levels for Acute Lymphoid Leukemia and Acute Myeloid Leukemia patients. The interleukin-15 serum levels were measured for 21 acute lymphoid leukemia patients and 21 acute myeloid leukemia patients compared to healthy people (24) as a control group using the ELISA Peprotech Company (USA), a protocol kit. The research data explain a significant decrease in interleukin-15 serum level for acute lymphoid leukemia (ALL) patients (99 pg/ml)compared with the healthy group (126 pg/ml) at level (P value=0.009), while the acute myeloid leukemia (AML) (141 pg/ml) patients recorded a nonsignificant increase in IL-15 serum level from the healthy group at (P>0.05). The data outcome clarified an important effect of acute lymphoid leukemia in reduced proinflammatory interleukin-15 serum level due to impairment in T and B lymphocyte production, which is correlated with immunosuppression response toward leukemia, while acute myeloid leukemia non-significantly increases the interleukin-15 serum level.

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  1. Zhang S, Zhao J, Bai X, Handley M, Shan F. Biological effects of IL-15 on immune cells and its potential for the treatment of cancer. Int Immunopharmacol. 2021;91:107318.
  2. Leonard WJ, Lin J-X, O'Shea JJ. The γc family of cytokines: basic biology to therapeutic ramifications. Immunity. 2019;50(4):832-50.
  3. Yang Y, Lundqvist A. Immunomodulatory effects of IL-2 and IL-15; implications for cancer immunotherapy. Cancers. 2020;12(12):3586.
  4. Knudson KM, Hodge JW, Schlom J, Gameiro SR. Rationale for IL-15 superagonists in cancer immunotherapy. Expert Opin Biol Ther. 2020;20(7):705-9.
  5. Meghnem D, Morisseau S, Frutoso M, Trillet K, Maillasson M, Barbieux I, et al. Cutting edge: Differential fine-tuning of IL-2–and IL-15–dependent functions by targeting their common IL-2/15Rβ/γc receptor. J Immunol. 2017;198(12):4563-8.
  6. Briukhovetska D, Dörr J, Endres S, Libby P, Dinarello CA, Kobold S. Interleukins in cancer: from biology to therapy. Nat Rev Cancer. 2021;21(8):481-99.
  7. Kubo H, Mensurado S, Gonçalves-Sousa N, Serre K, Silva-Santos B. Primary Tumors Limit Metastasis Formation through Induction of IL15-Mediated Cross-Talk between Patrolling Monocytes and NK CellsAntimetastatic Innate Response to Primary Tumors. Cancer Immunol Res. 2017;5(9):812-20.
  8. Yalcin A, Silay K, Balik AR, Avcioğlu G, Aydin AS. The relationship between plasma interleukin-15 levels and sarcopenia in outpatient older people. Aging Clin Exp Res. 2018;30(7):783-90.
  9. Waldmann TA, Dubois S, Miljkovic MD, Conlon KC. IL-15 in the Combination Immunotherapy of Cancer. Front Immunol. 2020;11:868.
  10. Robinson TO, Schluns KS. The potential and promise of IL-15 in immuno-oncogenic therapies. Immunol Lett. 2017;190:159-68.
  11. Waldmann TA, Miljkovic MD, Conlon KC. Interleukin-15 (dys) regulation of lymphoid homeostasis: Implications for therapy of autoimmunity and cancer. J Exp Med. 2020;217(1).
  12. Guo J, Liang Y, Xue D, Shen J, Cai Y, Zhu J, et al. Tumor-conditional IL-15 pro-cytokine reactivates anti-tumor immunity with limited toxicity. Cell Res. 2021;31(11):1190-8.
  13. Miao R, Lim VY, Kothapalli N, Ma Y, Fossati J, Zehentmeier S, et al. Hematopoietic stem cell niches and signals controlling immune cell development and maintenance of immunological memory. Front Immunol. 2020;11:600127.
  14. Rots D, Kreile M, Nikulshin S, Kovalova Z, Gailite L. Influence of IL15 gene variations on the clinical features, treatment response and risk of developing childhood acute lymphoblastic leukemia in Latvian population. Pediatr Hematol Oncol. 2018;35(1):37-44.
  15. Wang A, Zhong H. Roles of the bone marrow niche in hematopoiesis, leukemogenesis, and chemotherapy resistance in acute myeloid leukemia. Hematology. 2018;23(10):729-39.
  16. Terwilliger T, Abdul-Hay M. Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J. 2017;7(6):577.
  17. Kantarjian H, Kadia T, DiNardo C, Daver N, Borthakur G, Jabbour E, et al. Acute myeloid leukemia: current progress and future directions. Blood Cancer J. 2021;11(2):1-25.
  18. Çelik H, Lindblad KE, Popescu B, Gui G, Goswami M, Valdez J, et al. Highly multiplexed proteomic assessment of human bone marrow in acute myeloid leukemia. Blood Adv. 2020;4(2):367-79.
  19. Rubio-Jurado B, Sosa-Quintero LS, Carrasco-Martinez IL, Norato-Delgado A, Garcia-Luna E, Guzmán-Silahua S, et al. New biomarkers in non-Hodgkin lymphoma and acute leukemias. Adv Clin Chem. 2020;96:19-53.
  20. Fiore PF, Di Matteo S, Tumino N, Mariotti FR, Pietra G, Ottonello S, et al. Interleukin-15 and cancer: some solved and many unsolved questions. J Immunother Cancer. 2020;8(2).
  1. Sugimura R, Chao Y. Deciphering Innate Immune Cell-Tumor Microenvironment Crosstalk at a Single-Cell Level. Front Cell Dev Biol. 2022;10.
  2. Cierna Z, Smolkova B, Cholujova D, Gronesova P, Miklikova S, Cihova M, et al. Decreased levels of circulating cytokines VEGF, TNF-β and IL-15 indicate PD-L1 overexpression in tumours of primary breast cancer patients. Sci Rep. 2021;11(1):1-11.
  3. Santana Carrero RM, Beceren-Braun F, Rivas SC, Hegde SM, Gangadharan A, Plote D, et al. IL-15 is a component of the inflammatory milieu in the tumor microenvironment promoting antitumor responses. roc Natl Acad Sci. 2019;116(2):599-608.
  4. Wenjian L, Hua W, Weida W, Mengyuan Z, Chengcheng L, Yue L. High serum level of interleukin-15 predicts poor prognosis in adult standard-risk acute lymphoblastic leukaemia. American Society of Hematology Washington, DC; 2017.
  5. Moussa MM, Sheeba M, Mohsen EA, Elshazly M, Hussein NE. Assessment of serum interleukin-15 in adult acute leukemia patients (Egyptian sample). Egypt J Haematol. 2020;45(2):68.
  6. Verovskaya EV, Dellorusso PV, Passegué E. Losing sense of self and surroundings: hematopoietic stem cell aging and leukemic transformation. Trends Mol Med. 2019;25(6):494-515.