Analysis of Primary Chronic Lymphocytic Leukemia Cells’ Signaling Pathways

Skelin, Josipa; Matulić, Maja; Milković, Lidija; Heckel, Darko; Skoko, Jelena; Škreb, Kristina Ana; Jelić Puškarić, Biljana; Kardum-Skelin, Ika; Čičin-Šain, Lipa; Radić-Krišto, Delfa; Antica, Mariastefania (2024) Analysis of Primary Chronic Lymphocytic Leukemia Cells’ Signaling Pathways. Biomedicines, 12 (3). ISSN 2227-9059

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Abstract

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder characterized by a specific expansion of mature B-cell clones. We hypothesized that the disease has a heterogeneous clinical outcome that depends on the genes and signaling pathways active in the malignant clone of the individual patient. It was found that several signaling pathways are active in CLL, namely, NOTCH1, the Ikaros family genes, BCL2, and NF-κB, all of which contribute to cell survival and the proliferation of the leukemic clone. Therefore, we analyzed primary CLL cells for the gene and protein expression of NOTCH1, DELTEX1, HES1, and AIOLOS in both peripheral blood lymphocytes (PBLs) and the bone marrow (BM) of patients, as well as the expression of BCL2 and miRNAs to see if they correlate with any of these genes. BCL2 and AIOLOS were highly expressed in all CLL samples as previously described, but we show here for the first time that AIOLOS expression was higher in the PBLs than in the BM. On the other hand, NOTCH1 activation was higher in the BM. In addition, miR-15a, miR-181, and miR-146 were decreased and miR-155 had increased expression in most samples. The activation of the NOTCH pathway in vitro increases the susceptibility of primary CLL cells to apoptosis despite high BCL2 expression.

Item Type:	Article
Uncontrolled Keywords:	AIOLOS; NOTCH; BCL-2; CLL; leukemia; survival
Subjects:	BIOMEDICINE AND HEALTHCARE
Divisions:	Division of Molecular Biology Division of Molecular Medicine
Projects:	Project title Project leader Project code Project type Obnova timusa za preciznu medicinu u liječenju tumora i leukemija-THYMINNOVA Mariastefania Antica IP-2020-02-2431 HRZZ Znanstveni centar izvrsnosti za reproduktivnu i regenerativnu medicinu – istraživanja novih platormi i potencijala-CERRM Siniša Volarević; Slobodan Vukičević; Davor Ježek KK.01.1.1.01.0008 EK
Depositing User:	Ivana Vuglec
Date Deposited:	20 Oct 2025 12:39
URI:	http://fulir.irb.hr/id/eprint/10036
DOI:	10.3390/biomedicines12030524

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