The role of innate immune factors in acute myeloid leukemia before and after chemotherapy


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

The aim was to study the effect of chemotherapy on chemotaxis, as well as the expression of CXCL12, EGFR, CCR4 genes in mononuclear cells (MNCs) from patients with acute myeloid leukemia (AML) after CXCL12 exposure. Material and methods. Blood isolated from AML patients, as well as blood from healthy donors served as a clinical material. The study of chemotaxis was carried out using a Boyden chamber. CXCL12 was used as a chemoattractant. Gene expression was studied by means of using real-time polymerase chain reaction (RT-PCR). Results. Decreased chemotaxis of MNCs isolated from AML patients before chemotherapy started, in the direction towards CXCL12 was determined. An increase in the expression of the heterologous receptor CCR4 gene and a decrease in the expression of the EGFR gene before chemotherapy under the influence of CXCL12 were shown. After the therapy, the expression profiles change their direction. Conclusion. Above-described studies and obtained data demonstrate that there are existing other non-classical pathways of chemotaxis activation, as well as the possibility of cross-activation of heterologous receptors.

Full Text

Restricted Access

About the authors

Alexandra B. Vinnitskaya

I.I. Mechnikov Scientific Research Institute of Vaccines and Serums

Email: byzonka@yandex.ru
PhD, junior researcher 105064, Moscow, 5A Maly Kazenny Lane

Oksana A. Svitich

I.I. Mechnikov Scientific Research Institute of Vaccines and Serums; I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of Russia (Sechenov University)

Email: svitichoa@yandex.ru
MD, professor, corresponding member of RAS, professor of the Department of microbiology, virology and immunology of F.F. Erisman Institute of Public Health; Director 105064, Moscow, 5A Maly Kazenny Lane

Anatoly K. Golenkov

M.F. Vladimirsky Moscow Regional Research Clinical Institute

Email: golenkov@monikiweb.ru
MD, professor, head of the Clinic of clinical hematology and immunotherapy 129110, Moscow, 61/2 Shchepkina Str

Elena F. Klinushkina

M.F. Vladimirsky Moscow Regional Research Clinical Institute

head of the Department of clinical hematology and immunotherapy 129110, Moscow, 61/2 Shchepkina Str

Tatyana A. Zaitseva

I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of Russia (Sechenov University)

Email: zaytseva_t_a@staff.sechenov.ru
PhD, senior lecturer of the Department of microbiology, virology and immunology of F.F. Erisman Institute of Public Health 25009, Moscow, 11/10 Mokhovaya Str

Natalya V. Davydova

I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of Russia (Sechenov University)

Email: kaf-microb-pmgmu@yandex.ru
PhD, associate professor of the Department of microbiology, virology and immunology of F.F. Erisman Institute of Public Health 25009, Moscow, 11/10 Mokhovaya Str

Vitaly V. Zverev

I.I. Mechnikov Scientific Research Institute of Vaccines and Serums; I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of Russia (Sechenov University)

Email: zverev_v_v@staff.sechenov.ru
doctor of biological sciences, professor, academician of RAS, head of the Department of microbiology, virology and immunology of F.F. Erisman Institute of Public Health; scientific director 105064, Moscow, 5A Maly Kazenny Lane

References

  1. Lin W.W., Karin M.A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest. 2007; 117(5): 1175-83. doi: 10.1172/JCI31537.
  2. Coussens L.M., Werb Z. Inflammation and cancer. Nature. 2002; 420(6917): 860-67. doi: 10.1038/nature01322.
  3. Lacalle R.A., Blanco R., Carmona-Rodriguez L. et al. Chemokine receptor signaling and the hallmarks of cancer. Int Rev Cell Mol Biol. 2017; 331: 181-244. doi: 10.1016/bs.ircmb.2016.09.011.
  4. Chow M.T., Luster A.D. Chemokines in cancer. Cancer Immunol Res. 2014; 2(12): 1125-31. doi: 10.1158/2326-6066.CIR-14-0160.
  5. Филина А.Б., Свитич О.А., Аммур Ю.И. с соавт. Изучение миграционной способности мононуклеарных и опухолевых клеток относительно TLRs лигандов и CXCL12. Российский иммунологический журнал. 2017; 3: 545-547.
  6. Филина А.Б., Свитич О.А., Голенков А.К. с соавт. Альтернативные пути активации хемотаксиса клеток острого миелоидного лейкоза. Российский иммунологический журнал. 2019; 2: 596-598.
  7. Boyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968; 97: 77-89.
  8. Cancilla D., Rettig M.P., DiPersio J.F. Targeting CXCR4 in AML and ALL. Front Oncol. 2020; 10: 1672. doi: 10.3389/fonc.2020.01672.
  9. Ladikou E.E., Chevassut T., Pepper C.J., Pepper A.G. Dissecting the role of the CXCL12/CXCR4 axis in acute myeloid leukaemia. Br J Haematol. 2020; 189(5): 815-25. doi: 10.1111/bjh.16456.
  10. Kremer K.N., Peterson K.L., Schneider P.A. et al. CXCR4 chemokine receptor signaling induces apoptosis in acute myeloid leukemia cells via regulation of the Bcl-2 family members Bcl-XL, Noxa, and Bak. J Biol Chem. 2013; 288(32): 22899-914. doi: 10.1074/jbc. M113.449926.
  11. Drury L.J., Ziarek J.J., Gravel S. et al. Monomeric and dimeric CXCL12 inhibit metastasis through distinct CXCR4 interactions and signaling pathways. Proc Natl Acad Sci U S A. 2011; 108(43): 17655-60. doi: 10.1073/pnas.1101133108.
  12. Zhang Y., Tian L., Zheng Y. et al. C-terminal peptides of chemokine-like factor 1 signal through chemokine receptor CCR4 to cross-desensitize the CXCR4. Biochem Biophys Res Commun. 2011; 409(2): 356-61. doi: 10.1016/j.bbrc.2011.05.047.
  13. Boehrer S., Ades L., Braun T. et al. Erlotinib exhibits antineoplastic off-target effects in AML and MDS: a preclinical study. Blood. 2008; 111(4): 2170-80. doi: 10.1182/blood-2007-07-100362.
  14. Nath S., Bhattacharyya J., Sarma P.P. et al. The prognostic impact of epidermal growth factor receptor (EGFR) in patients with acute myeloid leukaemia. Indian J Hematol Blood Transfus. 2020; 36(4): 749-53. doi: 10.1007/s12288-020-01274-z.
  15. Deangelo D.J., Neuberg D., Amrein P.C. et al. A phase II study of the EGFR inhibitor gefitinib in patients with acute myeloid leukemia. Leuk Res. 2014; 38(4): 430-34. doi: 10.1016/j.leukres.2013.10.026.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2021 Bionika Media

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies