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Uncovering the Dysregulated RNA Binding Protein Network in Childhood Acute Myeloid Leukemia

Institution: 
Memorial Sloan-Kettering Cancer Center
Researcher(s): 
Michael Kharas, PhD
Grant Type: 
'A' Award Grants
Year Awarded: 
2016
Type of Childhood Cancer: 
Acute Myelogenous Leukemia (AML)
Project Description: 

Background 

Genetic alterations and epigenetic mechanisms can alter the balance of normal blood development resulting in hematological malignancies. Acute myeloid leukemia represents approximately 20% of all childhood leukemias. Despite a better prognosis for childhood leukemia compared to adults, 30% of children eventually fail to respond to therapy. An altered differentiation program that is accompanied by uncontrolled cell growth defines these leukemias. Comprehensive genetic and epigenetic mapping of pediatric myeloid leukemias have resulted in a heterogeneous and complex picture that characterizes this disease. However, one feature that correlates with the most aggressive myeloid leukemias is the gain of a self-renewal program that resembles features found in the normal hematopoietic stem cell. Our recent studies have uncovered a dysregulated RNA binding protein network in leukemia stem cells 

Project Goal

This proposal studies an RNA binding protein called SYNCRIP that is altered in myeloid leukemia. We have developed novel mouse genetic models in order to identify novel strategies for targeting the stem cell program in pediatric leukemias.

 

"We thank ALSF for their generous support that will allow our laboratory to continue to focus on researching the mechanisms that drive childhood leukemia. With this award, we will work toward a greater understanding of how an RNA binding protein can contribute to myeloid leukemia so that we can design novel therapeutic strategies and improve patient outcomes."