Chronic myeloid leukemia (CML) stem/progenitor cells (SPC) express a transcriptional program characteristic of proliferation, yet can achieve and maintain quiescence. Understanding the mechanisms by which leukemic SPC maintain quiescence can help to clarify how they persist during long-term targeted treatment. Researchers from the Beatson Institute for Cancer Research have recently identified a novel BCR-ABL1 protein kinase dependent pathway mediated by the up-regulation of hsa-mir183, the down-regulation of its direct target EGR1 and, as a consequence, up-regulation of E2F1.

The researchers show that inhibition of hsa-mir183 – detected by miRNA microarray, reduced proliferation and impaired colony formation of CML SPC. Downstream of this, inhibition of E2F1 also reduced proliferation of CML SPC, leading to p53-mediated apoptosis. In addition, they demonstrated that E2F1 plays a pivotal role in regulating CML SPC proliferation status.

Thus, for the first time, the mechanism of hsa-mir183/EGR1-mediated E2F1 regulation has been demonstrated as a novel, critical factor for CML SPC survival, offering new insights into leukemic stem cell eradication.


F. Pellicano, L. Park, K. R. Kranc, A. D. Whetton, T. L. Holyoake et al. (2018) Hsa-mir183/EGR1-mediated regulation of E2F1 is required for CML stem/progenitor cell survival Blood doi: 10.1182/blood-2017-05-783845 [abstract]

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