Česká společnost pro hmotnostní spektrometrii

(13. ročník České konference hmotnostní spektrometrie a 11. Neformální proteomické setkání - ThP-34)
Decoding Therapy-Induced Protein Subcellular Relocalization in Leukemia

Michaela Myšáková ^1 *, Kristýna Gloc Pimková ¹

1. BIOCEV, First Faculty of Medicine, Charles University

Abstrakt

Protein localization within cellular compartments is a tightly regulated process essential for proper protein functioning. Different localizations can affect protein activity, sometimes resulting in new functions. Recent studies have shown that anti-cancer treatment can induce protein relocalization, enabling them to acquire new functions that help cells survive the treatment. Such adaptive mechanisms play a major role in the development of cancer therapy resistance, which remains a challenge in the treatment of acute myeloid leukemia (AML). Our study explores how anti-leukemic therapy affects protein subcellular localization to uncover mechanisms that enable leukemic cells to withstand treatment.

To investigate this, we treated an AML cell line with the combination of hypomethylation therapy (5-azacytidine, AZA) and an inhibitor of anti-apoptotic protein BCL-2 (venetoclax, VEN). We applied the LOPIT-DC approach, which combines fractionation by differential ultracentrifugation, followed by isobaric labeling with tandem mass tags and LC-MS3 to untreated AML cells and AML cells treated with AZA and VEN. We identified 5,853 proteins and, using SVM-based prediction, we assigned 51% of proteins to specific cellular compartments. Our data revealed that AZA/VEN alters the subcellular localization of 215 proteins, identifying 12 relocalization events with high confidence (SVM score > 0.7). The proteins are crucial for protein stability, protein folding, and cellular division. Our findings highlight the potential of spatial proteomics to uncover how protein localization influences treatment response and resistance in AML.

* Korespondující autor: mysakovamichaela@gmail.com