TIAR and FMRP shape pro-survival nascent proteome of leukemia cells in the bone marrow microenvironment

• DOI: 10.1016/j.isci.2023.106543
• Publication Date: 2023-03-31T19:54:30Z
• Authors: Magdalena Wolczyk; Remigiusz Serwa; Agata Kominek; Agata Klejman; Jacek Milek; Marta Chwałek; Laura Turos-Korgul; Agata Charzyńska; Michal Dabrowski; Magdalena Dziembo...; Tomasz Skorski; Katarzyna Piwocka; Paulina Podszywal...
• Keywords: Proteome

Chronic myeloid leukemia (CML) cells circulate between blood and bone marrow niche, representing different microenvironments. We studied the role of two RNA-binding proteins, T-cell-restricted intracellular antigen (TIAR), fragile X mental retardation protein (FMRP) in regulation translation CML residing settings mimicking peripheral microenvironment (PBM) (BMM). The outcomes showed how conditions shaped process through TIAR FMRP activity, considering its relevance therapy resistance. QuaNCAT mass-spectrometric approach revealed that have a discrete modulatory effect on synthesis thus affect distinct aspects leukemic functioning hypoxic niche. In BMM setup, impacted metabolic adaptation substantially supported resistance to inhibition by homoharringtonine. Overall, our results demonstrated targeting post-transcriptional control should be considered when designing anti-leukemia therapeutic solutions.