Genes dependent on the dual-function protein β-catenin and the transcription factor Forkhead-Box-O3 (FOXO3) are expressed in the CD82+CD117+ cell fraction, which is “substantially enriched” with leukemia-initiating cells (LIC) in both MRD and early T-cell precursor acute lymphoblastic leukemia (ETP-ALL), Italian researchers report in a paper published in Blood in October. The findings “highlight key functional roles for β-catenin and FOXO3 and suggest novel therapeutic strategies to eradicate aggressive cell subsets in T-ALL,” they write.

A novel noncanonical functional interaction of β-catenin with FOXO3 “positively regulates LIC related genes, including the cyclin-dependent-kinase 4, which is a crucial modulator of cell cycle and tumor maintenance,” write Vincenzo Giambra, PhD, and colleagues at the Casa Sollievo della Sofferenza research hospital in Italy and the British Columbia Cancer Agency in Vancouver, Canada. Fluorescent reporters of β-catenin and FOXO3 in patient-derived xenografts identify minor subpopulations with enriched LIC activity.

While β-catenin is known to modulate LIC activity in T-ALL, its role in maintaining established leukemia stem cells has been largely unknown, the authors write. They add that “further studies will be required to explore the intriguing possibility that therapies which inhibit β-catenin and FOXO3 expression and/or activity may antagonize LIC activity and thereby improve clinicaloutcomes in T-ALL patients.”

• Panelli P, De Santis E, Colucci M, et al. Noncanonical β-catenin interactions promote leukemia-initiating activity in early T-cell acute lymphoblastic leukemia [published online ahead of print, 2022 Oct 31]. Blood. 2022;blood.2022017079. doi:10.1182/blood.2022017079

Tags: MRD, study, Treatment, leukemia, stem call, Research, T-ALL, Science, therapeutic, Clinical Research, gene, lymphoblastic leukemia, measurable residual disease