Research / Clinical
Summary
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Alice Yu, MD, PhD
Research Professor, Pediatrics
Hematologic Malignancies Program
Contact by Email
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Diseases/Research Topics
Leukemia, Neuroblastoma
Dr. Yu has been a long time member of the Pediatric Oncology Group (POG), which has evolved into Children’s Oncology Group (COG). She has served as a member of POG ALL biology Committee, T-cell Disease Committee, Neuroblastoma Disease Committee in the past, and currently COG Neuroblastoma Strategy Group.
Protocol Chair:
1. Chair of COG ANBL0032, A Phase III Randomized Study of Chimeric Anti-GD2 in High Risk Neuroblastoma Following Myeloablative Therapy and Autologous Stem Cell Rescue
2. Vice Chair of COG ADVL0222, A Phase II Study of Campath-1H in Children with Acute Lymphoblastic Leukemia in First or Subsequent Relapse
Progress in Biology Studies of T-ALL and Neuroblastoma:
Dr. Yu’s laboratory has served as a POG reference lab for studying biology of T-ALL and neuroblastoma. Her group found that two CDK inhibitors mapping to chromosome 9p21, p16 and p15, were inactivated almost universally in T-ALL. Also mapping to this region is the adenine/methionine salvage gene methylthioadenosine phosphorylase (MTAP), required for growth /survival of cells exposed to L-alanosine, an inhibitor of AMP synthesis. MTAP is deleted in 1/3 of T-ALL. These findings suggest that: 1) inactivation of both p16 and p15 are involved in the pathogenesis of T-ALL, 2) inhibition of cyclin Ds and CDK4/6 by UCN-01 may be therapeutic in ALL, 3) MTAP deficient ALL may be sensitive to L-alanosine an inhibitor of de novo synthesis of AMP. My in vitro studies confirmed that UCN-01 and alanosine may be useful agents for T-ALL, and analysis of p16 expression and MTAP respectively, may predict the responsiveness.
In contrast to T-ALL, studies of primary neuroblastoma showed significant p16 expression mRNA and protein levels. Interestingly, the samples in the unfavorable stage exhibited p16 mRNA and protein expression more frequently than those in the favorable stage. The prognostic significance of these findings is being pursued. In addition, her group is pursuing the role of micro-RNA in T-ALL and neuroblastoma.
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