Title of Research Grant

Altered Endocytosis in the Pathogenesis of Down Syndrome Leukemias


Catherine P. Lavau, DVM, PhD;
Associate Professor of Pediatrics
Duke University

Daniel S. Wechsler, MD, PhD
Chief, Hematology-Oncology
Duke University

Lay Summary of Research

While leukemia is a very rare disease in childhood, its frequency is dramatically increased in children with Down Syndrome (DS). The cause of this predisposition is not well understood. Endocytosis is the cellular process by which substances outside a cell (nutrients, growth factors) become internalized. Our laboratory has been investigating how altered endocytosis contributes to the onset of a subset of leukemias that carry particular gene mutations. We believe that impairment of endocytosis favors unrestrained cell proliferation, which can then contribute to increased numbers of leukemia cells. It has recently been shown that endocytosis is abnormal in cells from individuals with DS; this phenomenon is thought to underlie some of the cognitive impairment symptoms that are common in DS patients. In this proposal, we are interested in determining whether impairment of endocytosis is one of the changes that can lead to leukemia development in general, and in DS patients in particular.

We have developed methods to quantify endocytosis in cells, and we propose to study the effects of impairing endocytosis on cell proliferation, first in test tubes, and then in mice.

Next, using these same methods, we will explore whether leukemia (and other) cell lines derived from DS patients exhibit any defects in endocytosis, and how this correlates with increased cell proliferation. These studies will contribute to our understanding of some of the factors that are responsible for the high frequency of leukemias in children with DS, and potentially lead to new therapeutic approaches.