Defining the Role of a Novel, Developmentally Restricted Hematopoietic Stem Cell in Pediatric Leukemias

Project Goal
The goal of this project is to identify the root cause of blood cancer in infants and children. We are focusing on understanding how the most common and aggressive form of infant blood cancer, B-cell acute lymphocytic leukemia (B-ALL), arises before or soon after birth in some children. Understanding the cause of this disease will enable the design of drugs that specifically eliminates cancer cells, without causing damage to the body's healthy cells.

Avoiding side effects is particularly important in children as their growing bodies are much less able to tolerate standard chemotherapy. The idea of specific drug targeting is based on the success with the drug Gleevec in treating patients with chronic myelogenous leukemia (CML). Because it is extremely difficult to study leukemia in children before they are born, much less is known about the causes of cancer in infants than in adults, but it is known that most cases of leukemia in infants are caused by mutations in a gene called MLL.

We have identified a cell type present only during prenatal development that has properties similar to the cells present in kids with MLL-induced leukemia. We believe that MLL mutations in this cell type leads to infant leukemia. Here, we propose to define the properties of this cell type and to determine whether give rise to cancer when MLL is mutated the same way as in infant leukemia. Our results will help identify drugs that, similar to Gleevec, avoid devastating side effects while curing children with cancer.