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In CML, somatic\n                    <jats:italic>RUNX1<\/jats:italic>\n                    mutations and\n                    <jats:italic>RUNX1::MECOM\/EVI1<\/jats:italic>\n                    , are associated with TKI resistance and progression to BP-CML. To examine post-transcriptional dysregulation downstream of\n                    <jats:italic>RUNX1<\/jats:italic>\n                    aberrations, we used orthogonal organic phase separation to characterise the RNA-binding proteome of RUNX1 deficient BP-CML cells. RUNX1 depleted BP-CML cells exhibited significant alterations to RBPs involved in stress response pathways and translation\/ribosome-biogenesis. Furthermore, RUNX1 depletion or expression of RUNX1::EVI1 in BP-CML cells induced expression and RNA binding activity of SPATS2L, a component of stress granules (SG). Whilst RUNX1 depletion increased SG-assembly, SPATS2L depletion reduced SG-assembly and inhibited the growth\/survival of multiple BP-CML cell lines. Homoharringtonine (HHT), used historically in TKI-resistant CML, ablated SG-assembly in BP-CML cells with RUNX1 depletion, and primary BP-CML cells with LOF\/hypomorphic\n                    <jats:italic>RUNX1<\/jats:italic>\n                    mutations were preferentially sensitised to HHT. Suppressing SPATS2L expression induced by RUNX1 depletion, reduced SG-forming capacity and increased the HHT-sensitivity of RUNX1 depleted BP-CML cells, suggesting SPATS2L contributes to therapeutic resistance in\n                    <jats:italic>RUNX1<\/jats:italic>\n                    mutated CML. Finally, we demonstrate that SGs may contribute more widely to TKI-resistance in this setting. This study suggests that SPATS2L\/SG induction could be critical to\n                    <jats:italic>RUNX1<\/jats:italic>\n                    -mutant leukemias, and, provides preliminary evidence for a mutationally-targeted approach in CML with\n                    <jats:italic>RUNX1<\/jats:italic>\n                    aberrations.\n                  <\/jats:p>","DOI":"10.1038\/s41375-026-03161-4","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T09:52:22Z","timestamp":1791539542000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["RUNX1 aberrations in blast-phase chronic myeloid leukaemia induce the RNA-binding protein SPATS2L, which promotes growth, survival and stress granule assembly"],"prefix":"10.1038","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0884-995X","authenticated-orcid":false,"given":"D. 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