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

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

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Leukocyte, Permanent Cell Line Cell, Cell Culture

DISEASE(S): Chronic Myeloid Leukemia

SUBMITTER: Remigiusz Serwa  

LAB HEAD: Dr Paulina Podszywalow-Bartnicka

PROVIDER: PXD032332 | Pride | 2023-05-10

REPOSITORIES: Pride