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Registration Number

0225U004310, (0124U003787) , R & D reports

Title

Activation of signaling cascades for the elimination of transformed B cells in chronic lymphocytic leukemia

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З’ясування ролі цитокінів опосередкованих сигнальних каскадів у патобіології трансформованих В-клітин при ХЛЛ.

Head

Kovalevska Larysa M., Кандидат біологічних наук

Registration Date

28-11-2025

Organization

R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology National Academy of Sciences of Ukraine

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The aim of the proposed project is to identify the mechanisms of inhibition of apoptosis and activation of mature B lymphocytes in CLL for the development of personalized therapy based on the identification of key players of the main signaling cascades, which are involved in blocking the response of B cells to external signals of the immune system of the patient's body.

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At the second stage, it was found that TGFB and IL-2 indirect signaling cascades play a significant role in the pathobiology of transformed B cellsat CLL, as a significant decrease in the expression of key transcription factors was detected - PU.1, EBF1, Spi-B, BLIMP1, Bcl6, IRF4 and IRF8, which indicates a complex disruption of several critical stages of B cell development, including the early stages of plasma cell maturation and differentiation. Simultaneous preservation of IL1 levels, almost complete absence of IL6 and reduced expression of IL17 complement the overall picture of dysfunction of cytokine regulation, which has been repeatedly emphasized in modern international studies of CLL. Of particular interest are the data on the complete absence of STAT3 and STAT5B expression, a sharp decrease in STAT5A and a heterogeneous profile of STAT6, since proteins of the STAT family are considered critical mediators of survival and plasticity of tumor B cells. Our results extend existing insights by demonstrating the systemic nature of disruptions in both the transcriptional program and cytokine signaling pathways, which together form the basis for increased adaptability and potential therapeutic resistance of leukemic cells.

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Iryna A. Kriachok
Tytorenko Iryna B.
Trembach Liudmyla V.
Nataliia Y. Lukianova
Matvieieva Alina S.
Kalman Serhii S.
Vozniuk Liudmyla V.

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2025-11-28