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Massey researcher awarded $3 million to study the effect of blood cell stimulation on the development of adolescent leukemia and bone marrow disorders

May 24, 2016


Massey program leader, researcher and physician Seth Corey M.D., M.P.H., was awarded more than $3 million in grant funding from the National Heart, Lung and Blood Institute (NHLBI) for a four-and-a-half-year study on the evolution of a blood cell deficiency to pre-leukemia. The research aims to determine whether a common treatment for the condition acts as a contributor to the development of leukemia or other life-threatening bone marrow disorders.

Corey, who is co-leader of the Cancer Molecular Genetics research program at VCU Massey Cancer Center, the Children's Hospital Foundation Endowed Chair in Pediatric Cancer Research, and chief of pediatric hematology, oncology and stem cell transplantation at Massey and Children’s Hospital of Richmond at VCU, will study severe congenital neutropenia (SCN), a condition that involves a deficiency of granulocytes, which are white blood cells that have a crucial role in fighting infections. This shortage of white blood cells is often recognizable at birth or shortly afterward and leads to recurrent infection starting early in childhood.

Life-threatening infections in children with SCN can be avoided through the use of a recombinant granulocyte colony-stimulating factor (GCSF), which increases the number of white blood cells. However, roughly 30 percent of children with SCN develop leukemia or a myelodysplastic syndrome (MDS) during adolescence. Myelodysplastic syndromes are a group of life-threatening blood and bone marrow disorders that progress into more deadly forms, and they increase in regularity as the population ages.

One of the major clinical questions prompting this study is whether long-term treatment with GSCF contributes to the transformation of SCN into MDS or acute myeloid leukemia (AML). The research will examine the nature of SCN and how it evolves into both pre-malignant and malignant states, specifically focusing on the competition between clones of normal and abnormal blood cells.

Necessary for the successful investigation of this evolution is evaluating the mutation of a GCSF receptor, and using that knowledge to determine the biochemical and genetic changes that occur during the evolution and how those changes contribute to the evolution.

The resulting information will be used to create a mathematical model that can calculate future circumstances and occurrences of this malignant transformation.

“Our goal is to understand how myelodysplastic syndromes and myeloid malignancies evolve from flawed or injured blood stem cells. We can use our mathematical model to predict when and in whom malignant evolution will occur, and then intervene earlier with stem cell transplantation,” Corey said.

Stem cell/bone marrow transplantation is the only form of treatment that can cure MDS, and it is also a common form of treatment for AML.

The NHLBI awarded the grant, totaling $3,091,306 through March 2020, while Corey was at Northwestern University in September 2015, and it was officially transferred over to VCU in May 2016.

Corey joined VCU in October 2015.  He is also a professor of pediatrics and microbiology/immunology at the VCU School of Medicine.

Corey is collaborating on this study with Rosemary Braun, Ph.D., M.P.H., of Northwestern University Feinberg School of Medicine; Marek Kimmel, Ph.D., M.S., from the Rice University George R. Brown School of Engineering; and Garry Nolan, Ph.D., of the Stanford School of Medicine.

Written by: Blake Belden

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