ISSN 1866-8836
Клеточная терапия и трансплантация

CM-03. Regulation of TIM-3 expression in myeloid neoplasms

Anna N. Parfenenkova, Ildar M. Barkhatov, Olga S. Epifanovskaya, Alena I. Shakirova, Nikolai Yu. Tcvetkov, Elena V. Babenko, Kirill V. Lepik, Elena V. Morozova, Ivan S. Moiseev

RM Gorbacheva Research Institute, Pavlov University, St. Petersburg, Russia

Dr. Anna N. Parfenenkova, phone: +7 (951) 684-61-30, e-mail:

doi 10.18620/ctt-1866-8836-2021-10-3-1-148


Myelodysplastic syndrome (MDS) is a heterogeneous clonal disease characterized by the presence of cytopenia in the peripheral blood and dysplasia in the bone marrow. The rate of progression to acute myeloid leukemia (AML) is significant and the median time to progression varies from months to years according to biological and clinical features. Recent preclinical and clinical research indicated the significance of TIM-3 signaling checkpoint pathways in the progression of MDS and AML and showed the utility of TIM-3 inhibition with monoclonal antibodies in inducing clinical remission.


During the study it was found that addition of AKT inhibitor MK-2206 to THP-1 cells at concentrations of 5 and 10 μM decreased the level of TIM-3 at the membrane surface. This was also confirmed on the bone marrow of a patient transformed from MDS to AML. In 3 out of 15 patients with high-risk MDS, mutations in the RUNX1 gene were found and associated with increased levels of TIM-3 expression on CD3+CD8+ cells of the tumor microenvironment, as well as less OS, compared with high-risk MDS patients without mutations.


A promising direction for further research is to study the effectiveness of AKT suppression using MK-2206 both in patients with high-risk MDS with mutations in RUNX1 and in those who are transformed into AML.


TIM-3, checkpoint inhibitors, myeloid neoplasms.

Volume 10, Number 3

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doi 10.18620/ctt-1866-8836-2021-10-3-1-148

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