Unravelling the molecular role of the long non-coding RNA FAM30A in modulating acute myeloid leukaemia stem cells dynamics

Abstract

Acute myeloid leukaemia (AML) is the most common adult leukaemia, driven by malignant myeloid precursors and sustained by resistant leukaemia stem cells (LSCs). Long non coding RNAs have emerged as key regulators, with FAM30A strongly linked to poor prognosis and LSC activity. This work reveals that FAM30A depletion reduces viability, enhances apoptosis, increases chemotherapy sensitivity, promotes differentiation, and prevents bone marrow engraftment. Conversely, FAM30A overexpression boosts stemness, proliferation, chemoresistance, and engraftment. Mechanistically, FAM30A interacts with MSI2, influencing the regulation of stem cell-specific RUNX1 isoforms. RUNX1 activation was shown to depend on both FAM30A and MSI2, forming a feedback loop that sustains LSCs. These insights position FAM30A as a central regulator of AML stem cell biology and highlight a novel pathway that could be therapeutically targeted to overcome relapse and resistance.