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Function of the PR Domain of the MDSI-EVI1 in MLL Fusion Protein Leukemogenesis

University of Rochester
Archibald Perkins, MD, PhD
Grant Type: 
Springboard Grants
Year Awarded: 
Type of Childhood Cancer: 
Acute Lymphoblastic Leukemia (ALL), Acute Myelogenous Leukemia (AML)
Project Description: 


Leukemia is the most common form of cancer among children and adolescents, and approximately 2,000 infants within their first year of life developed life threatening acute leukemia in the United States. The presence of the MLL (Mixed Lineage Leukemia) gene translocation is the most significant independent factor associated with poor outcome and high risk of relapse in infant leukemia.

Project Goal

Our goal is to devise new and effective treatments through the study of how MLL subverts cellular growth control.

Update 4/2015

Several years ago, we made the remarkable discovery that, in a mouse model for a lethal form of infant leukemia, when we eliminated one specific protein called MDS1-EVI1 or ME for short; also known as PRDM3), all of the leukemia cells died, significantly extending the life of the mice. We recognized immediately that this meant that if we can inhibit the activity of this protein, we could potentially cure leukemia. Fortunately, there was good reason to think that we could inhibit this activity, since the protein had all of the hallmarks of other proteins that had successfully been targeted by drug companies (see http://www.epizyme.com/programs/dot1l-inhibitor/). Thus, we are very excited and optimistic about the prospect that ME/PRDM3 can be inhibited by a drug, and that this drug can cure certain forms of infant leukemia.

There are many steps involved to get to this goal, and thanks to funds from ALSF, we made significant progress in the past year and a half. One key step is to develop an "assay" for the protein, and we have had recent success in that direction, both in the test tube and in a cultured dish of cells. On a third area -- determining the structure of ME/PRDM3, things are moving more slowly, and more work is needed. Nonetheless, we are unbowed, and will continue on. Importantly, the funds from ALSF have resulted in our success in receiving a grant from the National Institutes of Health to continue this research.