Naslov
Bone marrow stromal cells inhibit monocytic differentiation induced by low-dose cytarabine

Autori
Smoljo, Tomislav ; Tomić, Barbara ; Lalić, Hrvoje ; Dembitz, Vilma ; Višnjič, Dora

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Annual meeting of the Croatian Immunological Society 2022: Book of Abstracts / Wensveen, Felix M. ; Kavazović, Inga - Rijeka : Hrvatsko imunološko društvo, 2022, 64-64

Skup
Annual meeting of the Croatian Immunological Society 2022

Mjesto i datum
Sveti Martin na Muri, Hrvatska, 06.10.2022. - 08.10.2022

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
monocytic differentiation, stromal cells, low-dose cytarabine

Sažetak
Bone marrow stromal (BMS) cells form niche that regulates both normal and malignant myeloid differentiation. Our previous studies showed that low-dose cytarabine (LDAC) and pyrimidine synthesis inhibitors, 5-aminoimidazole-4- carboxamide ribonucleoside (AICAr) and brequinar, induce differentiation in acute myeloid leukemia (AML) cells by activating checkpoint kinase 1 (Chk1). The murine stromal cell line MS-5 in known to attenuate cytarabine-induced killing of AML cells, but the effects on cytarabine- induced differentiation are unknown. Present study investigates the effects of differentiation agents in a co-culture of BMS MS-5 and AML U937 cell lines. Results show that the presence of MS-5 cells reduces toxicity and S-phase arrest caused by differentiation agents in U937 cells. However, the expression of differentiation marker CD11b decreases only in U937 cells treated with LDAC and preliminary data from transwell experiments suggest that these effects do not depend on cell- to-cell contact. Both AICAr and high-dose cytarabine inhibit the growth of MS-5 cells, and AICAr induced their fibrocyte-like morphology. The addition of nucleosides completely prevents the effects of AICAr and brequinar on cell cycle and differentiation of AML cells, but has no effects on AICAr-induced changes in BMS cells. Preliminary data suggest that AICAr activates AMP-activated kinase (AMPK) and inhibits mammalian target of rapamycin (mTOR) in MS-5 cells. In conclusion, BMS decreases differentiation of AML cells in response to LDAC. AICAr induces fibrocyte-like changes of stroma independent of pyrimidine synthesis inhibition. These results suggest that mechanisms responsible for phenotypic changes induced by AICAr differ in AML and stromal cells.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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