Uncovering the Pathology of a Rare Pediatric Leukemia
Credit: Northwestern Medicine
A team of scientists has demonstrated the mechanism by which ETO2-GLIS2, a gene fusion, promotes the development of an aggressive form of pediatric leukemia. The findings, published in Cancer Cell, also reveal an opportunity for the development of therapeutics.
The study was co-authored by John Crispino, PhD, the Robert I. Lurie, MD, and Lora S. Lurie Professor of Medicine in the Division of Hematology and Oncology.
Acute megakaryoblastic leukemia (AMKL), a rare type of blood cancer predominantly found in children, has two major pediatric subgroups: AMKL in patients with Down syndrome and those without. While the disease in those with Down syndrome (DS) is relatively well-defined and carries a good prognosis, non-DS AMKL is much less well-understood.
Recently, scientists discovered that a gene fusion called ETO2-GLIS2 — produced by an inversion on chromosome 16 — is present in 20 to 30 percent of cases of non-DS AMKL, and is associated with a very poor patient prognosis. But up until now, it was unclear exactly how this gene fusion blocks normal cell differentiation, a hallmark of leukemia.
In the current study, the scientists illustrated how ETO2-GLIS2 induces an irregular transcription network that underlies AMKL. They further demonstrated that expression of a peptide that inhibits ETO2-GLIS2 oligomerization could release the differentiation block — insights which could inform the development of novel therapeutics.
“Acute megakaryoblastic leukemia is a devastating blood cancer that requires new targeted and efficacious therapies,” Crispino said. “The discovery of the mechanism by which ETO2-GLIS2 fusion promotes leukemia provides important new insights into ways to target these malignant cells.”
This article has been republished from materials provided by Northwestern Medicine. Note: material may have been edited for length and content. For further information, please contact the cited source.
Thirant, C., Ignacimouttou, C., Lopez, C. K., Diop, M., Mouël, L. L., Thiollier, C., . . . Mercher, T. (2017). ETO2-GLIS2 Hijacks Transcriptional Complexes to Drive Cellular Identity and Self-Renewal in Pediatric Acute Megakaryoblastic Leukemia. Cancer Cell, 31(3), 452-465. doi:10.1016/j.ccell.2017.02.006
Researchers Awarded $28M for Illuminating Druggable Genome NIH GrantsNews
Researchers receive grants as part of the NIH program focused on experimental and informatics approaches to characterize understudied proteins from three gene families: ion channels, G protein-coupled receptors (GPCRs), and protein kinases.READ MORE
PhoreMost Completes $15M (£11M) Series-A Round to Enter Drug DiscoveryNews
Investment to fund expansion of operations and progression of drug target pipeline.READ MORE
Nanoparticles Derived from Tea Leaves Destroy Lung Cancer CellsNews
Nanoparticles derived from tea leaves inhibit the growth of lung cancer cells, destroying up to 80% of them, new research by a joint Swansea University and Indian team has shown.