Hoxworth and Children's researchers help identify signals to suppress expression of anti-leukemic genes

Researchers at University of Cincinnati (UC) Hoxworth Blood Center, the UC Academic Health Center and Cincinnati Children’s are among a group led by Jose Cancelas, MD, PhD, director of Hoxworth Blood Center, to identify the key signals that suppress the expression of anti-leukemic genes in cells. The study, titled “The Signaling Axis Atypical Protein Kinase C λ/ι-Satb2 Mediates Leukemic Transformation of B-Cell Progenitors” was published online in the Jan. 4, 2019 edition of Nature Communications.

Cancelas says lymphoblastic leukemia is the most common cancer in children and identifying these signals could lead to improved outcomes for those patients.

“A type of lymphoblastic leukemia composed by mutations that result in common signals—named Philadelphia/Philadelphia-like—is the most frequent in people under the age of 40,” says Cancelas. “Despite the development of some drugs, the overall outcome of these patients is poorer than for other types of lymphoblastic leukemia.”

Cancelas says that upstream leukemic mutations activate the atypical protein kinase C-type iota and the chromatin modifier Satb2, which is a repressor of genes important in normal differentiation of B lymphocytes. Inhibition of these downstream signals, either genetically or with specific drugs, results in leukemia eradication through impairing the proliferation, survival and especially the differentiation arrest of leukemic progenitors.

The Cancelas-led group in Cincinnati collaborated with Maria Diaz-Meco, PhD, Jorge Moscot, PhD and Miguel Reina-Campos, all at the Sanford Burnham Prebys Medical Discovery Institute in La Jolla, California. Other investigators include Ramesh Nayak, PhD, Shailaja Hedge, PhD and Mark Althoff at the Cancelas Research Lab at Cincinnati Children’s and Fatima Mohmoud at Hoxworth. The research team also includes Ashley Wellendorf, John Perentesis, MD, Damien Reynaud, PhD, Yi Zheng, PhD, all at Cincinnati Children’s.

This study has been partly supported by the National Blood Foundation, National Institutes of Health F31HL1324801, R01CA172025, R01CA207177, R01GM110628, United States Department of Defense, Leukemia and Lymphoma Society of North America and Williams Lawrence & Blanche Hughes Foundation. The authors declare no conflicts of interest.