Acute Myeloid Leukemia Patient-Derived Xenograft Models Generated with the Use of Immunodeficient NSG-SGM3 Mice

AUTOIMMUNE THROMBOCYTOPENIA

EV Baidyuk1, EV Belotserkovskaya1, LL Girshova1,2, VA Golotin1, KA Levchuk2, ML Vasyutina2, YaA Portnaya1, EV Shchelina2, OG Bredneva2, AV Petukhov1,2,3, AYu Zaritskey2, ON Demidov1,3

1 Institute of Cytology, 4 Tikhoretskii pr-t, Saint Petersburg, Russian Federation, 194064

2 VA Almazov National Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341

3 Sirius University of Science and Technology, 1 Olimpiiskii pr-t, Sochi, Russian Federation, 354340

For correspondence: Ekaterina Viktorovna Baidyuk, PhD in Biology, 4 Tikhoretskii pr-t, Saint Petersburg, Russian Federation, 194064; e-mail: katya_bay@mail.ru; Ekaterina Vasilevna Belotserkovskaya, PhD in Biology, 4 Tikhoretskii pr-t, Saint Petersburg, Russian Federation, 194064; e-mail: belotserkovskaya.ev@gmail.com

For citation: Baidyuk EV, Belotserkovskaya EV, Girshova LL, et al. Acute Myeloid Leukemia Patient-Derived Xenograft Models Generated with the Use of Immunodeficient NSG-SGM3 Mice. Clinical oncohematology. 2021;14(4):414–25. (In Russ).

DOI: 10.21320/2500-2139-2021-14-4-414-425

ABSTRACT

Background. Up to the present the survival rates of acute myeloid leukemia (AML) patients have remained low. A successful OML management presupposes generating personalized models of the disease. The most promising research activity in this field is creation of AML patient-derived xenograft models using the advanced strain of immunodeficient humanized NSG-SGM3 mice.

Aim. To generate AML patient-derived xenograft models using immunodeficient NSG-SGM3 mice.

Materials & Methods. The creation of PDX models was based on bone marrow aspirates taken from 4 patients with newly diagnosed AML who were treated at the VA Almazov National Medical Research Center. Patient-derived tumor cells were transplanted to NSG-SGM3 mice. Test experiment consisted in injecting AML cells OCI-АМL2 and HL60 in NSG-SGM3 mice. The efficacy of tumor engraftment was evaluated in terms of physical condition of animals and laboratory tests (blood count, blood smear, PCR, and flow cytofluorometry).

Results. The engraftment of applied tumor cells derived from 4 AML patients was achieved in half (2 out of 4) of the mice. In 2 mice with successful transplantation leukocytosis was reported. Blast cells were identified in peripheral blood on Day 30 after transplantation. The mice with injected AML cells OCI-АМL2 and HL60 showed a more aggressive course of disease. Among tested approaches to evaluate tumor engraftment in mouse recipients, the PCR method was marked by highest sensitivity.

Conclusion. The use of immunodeficient humanized NSG-SGM3 mice enables successful generation of AML patient-derived xenograft models.

Keywords: xenograft model, immunodeficient humanized mice, AML, NSG-SGM3 mice.

Received: April 27, 2021

Accepted: August 1, 2021

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Статистика Plumx английский

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