RUNX1 aberrations linked to SPATS2L-mediated stress granule assembly in blast-phase CML

RUNX1 aberrations are associated with tyrosine kinase inhibitor (TKI) resistance and progression to blast-phase chronic myeloid leukaemia (BP-CML). In a laboratory study published in Leukemia, researchers used orthogonal organic phase separation to characterise the RNA-binding proteome of RUNX1-deficient BP-CML cells. Experiments in cell lines and primary BP-CML cells examined stress granule assembly, growth, survival and drug sensitivity; sample counts were not provided in the supplied abstract.

RUNX1 depletion altered RNA-binding proteins involved in stress responses and translation/ribosome biogenesis. Both RUNX1 depletion and RUNX1::EVI1 expression increased SPATS2L expression and RNA-binding activity. Depleting SPATS2L reduced stress granule assembly and inhibited growth and survival across multiple BP-CML cell lines.

Homoharringtonine abolished stress granule assembly in RUNX1-depleted cells, and primary cells carrying loss-of-function or hypomorphic RUNX1 mutations were preferentially sensitised to the drug. Suppressing SPATS2L also increased homoharringtonine sensitivity in RUNX1-depleted cells. These findings suggest a potential mechanism of therapeutic resistance and a mutation-directed treatment strategy, but remain preclinical. The supplied abstract reports no quantitative effect sizes or patient treatment outcomes, and does not establish clinical benefit.