Chemotherapy effect on arginine / citrulline cycle indicators in patients with acute myeloid leukemia and concomitant obesity.
DOI:
https://doi.org/10.26641/2307-0404.2020.2.206378Keywords:
arginine, citrulline, ornithine decarboxylase, arginase, acute myeloid leukemia, obesityAbstract
The aim of study was to investigate the changes in the arginine / citrulline cycle in patients with acute myeloid leukemia (AML) with concomitant obesity in dynamics of chemotherapy (CT). The study included 20 patients with newly diagnosed AML who had a body mass index (BMI) above 25. The average BMI was 29.35±0.93 kg/m2. Patients have undergone a course of remission induction CT "7+3" or "5+2". All patients were examined twice: before CT and on the 28th day. Complete blood test was assessed. Arginine and citrulline content, arginase and ornithine decarboxylase (ODC) activity were measured in the blood serum. The study results showed a 3-fold decrease in arginine content in the blood serum of patients with AML, as well as a 3.9-fold increase in arginase activity, 1.9-fold – ODC, 7.6-fold higher citrulline concentration compared with control (p<0.05). After CT, against the background of complete blood count normalization in AML patients with concomitant obesity, a 1.3-fold decrease in arginine concentration was noted, while the arginase activity increased by 2.2 times, ODC activity – by 1.8 times and citrulline content – by 2.4 times (р<0.05). After CT a high direct correlation between BMI and arginine concentration in AML patients with concomitant obesity (r=+0.63; p<0.05), as well as between the activity of ODC and arginine content (r=+0,55; p<0.05) was revealed.Thus, in AML patients with obesity prior to CT the disorders in the arginine / citrulline cycle were present, which are caused by oncohematological disease. Excess weight and obesity affect serum arginine levels, which may contribute to chemotherapy resistance.References
Antomonov MYu. [Mathematical processing and analysisof biomedical data]. Medinform. 2018:579. Russian.
Skrypnyk IM, Maslova HS. [Evaluation of the frequency of development and nature of hepatotoxic reactions in patients with acute leukemia in the dynamics of remission induction]. Suchasna hastroenterolohiia. 2018;2(100):16-22. Ukrainian.
Styuart Dzh, Yang Dzh, Shvachkina YuP, editor. Translation from English. Mishina GP. [Solid-phase synthesis of peptides]. Moskva: Mir; 1971. p. 129-30. Russian.
Khramov VA, Listopad GG. [Modification of the Chinard ornithine method and its use for the quantification of serum arginase]. Laboratornoe delo. 1973;10:591-2. Russian.
Khramov VA. [A simple method for determining the activity of ornithine decarboxylase in mixed human saliva]. Klinicheskaya laboratornaya diagnostika. 1997;4:14-5. Russian.
Heuser M, Ofran Y, Boissel N, Mauri SB, Craddock C, Janssen J, et al. Acute myeloid leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020;S0923-7534(20):36079-8. doi: https://doi.org/10.1016/j.annonc.2020.02.018
Caldwell RW, Rodriguez PC, Toque HA, Narayanan SP, Caldwell RB. Arginase: a multifaceted enzyme important in health and disease. Physiol Rev. 2018;98(2):641-65. doi: https://doi.org/10.1152/physrev.00037.2016
Mussai F, Egan S, Higginbotham-Jones J, Perry T, Beggs A, Odintsova E, et al. Arginine dependence of acute myeloid leukemia blast proliferation: a novel therapeutic target. Blood. 2015;125(15):2386-96. doi: https://doi.org/10.1182/blood-2014-09-600643
Boyde TR, Rahmatullah M. Optimization of Conditions for the Colorimetric Determination of Citrulline, Using Diacetyl Monoxime. Analytical Biochemistry. 1980;107:424-31.
Lam SK, U KP, Li YY, Xu S, Cheng PN, Ho JC. Inhibition of ornithine decarboxylase 1 facilitates pegylated arginase treatment in lung adenocarcinoma xenograft models. Oncology Reports. 2018;40(4):1994-2004. doi: https://doi.org/10.3892/or.2018.6598
Orgel E, Mueske NM, Sposto R, Gilsanz V, Freyer DR, Mittelman SD. Limitations of body mass index to assess body composition due to sarcopenic obesity during leukemia therapy. Leuk Lymphoma. 2018;59(1):138-45. doi: https://doi.org/10.3109/10428194.2015.1136741
Castillo JJ, Mulkey F, Geyer S, Kolitz JE, Blum W, Powell BL, et al. Relationship between obesity and clinical outcome in adults with acute myeloid leukemia: A pooled analysis from four CALGB (Alliance) clinical trials. Am J Hematol. 2016;91(2):199-204. doi: https://doi.org/10.1002/ajh.24230
De Santo C, Booth S, Vardon A, Cousins A, Tubb V, Perry T, et al. The arginine metabolome in acute lymphoblastic leukemia can be targeted by the pegylated-recombinant arginase I BCT-100. Int J Cancer. 2018;142(7):1490-502. doi: https://doi.org/10.1002/ijc.31170
Downloads
How to Cite
Issue
Section
License
Copyright (c) 2020 Medicni perspektivi (Medical perspectives)
This work is licensed under a Creative Commons Attribution 4.0 International License.
Submitting manuscript to the journal "Medicni perspektivi" the author(s) agree with transferring copyright from the author(s) to publisher (including photos, figures, tables, etc.) editor, reproducing materials of the manuscript in the journal, Internet, translation into other languages, export and import of the issue with the author’s article, spreading without limitation of their period of validity both on the territory of Ukraine and other countries. This and other mutual duties of the author and all co-authors separately and editorial board are secured by written agreement by special form to use the article, the sample of which is presented on the site.
Author signs a written agreement and sends it to Editorial Board simultaneously with submission of the manuscript.
