Transfer of IGF2BP3 Through Ara-C-Induced Apoptotic Bodies Promotes Survival of Recipient Cells

Transfer of IGF2BP3 Through Ara-C-Induced Apoptotic Bodies Promotes Survival of Recipient Cells

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Cytosine arabinoside (Ara-C) has been the standard therapeutic agent for myelodysplastic syndromes (MDS) and adult acute myeloid leukemia (AML) patients for decades.Considerable progress has been made in development of new treatments for MDS/AML patients, but drug resistance remains a major clinical problem.Apoptotic bodies (ABs), produced by late apoptotic cells, can enclose bioactive components that affect cell-cell interactions and disease progression.

We isolated and identified drug-induced ABs from Ara-C-tolerance cells.Treatment of sensitive cells with Ara-C-induced ABs resulted in Ara-C-resistant phenotype.We further Kids Apparel investigated components and functions of Ara-C-induced ABs.

Proteomics analysis in combination with mass spectrometry revealed that Ara-C-induced ABs carried numerous RNA-binding proteins, notably including insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3).Delivery of AB-encapsulated IGF2BP3 promoted survival of recipient cells by activating PI3K-AKT and p42-44 MAPK pathways.High IGF2BP3 level in ABs from MDS/AML patient plasma was correlated with poor overall survival.

Our findings demonstrate that AB-derived IGF2BP3 plays an essential role in acquired Ara-C resistance in MDS/AML patients, and is a potential therapeutic Gearbox Coupling target for suppression of Ara-C resistance.