Looking for new targets to enhance the therapy for childhood Ph+ acute lymphoblastic leukemia
Research Assistant Professor
Background and Significance
Acute lymphoblastic leukemia involving the Philadelphia chromosome (Ph+ ALL) is among the most difficult types of ALL to cure. BCR-ABL tyrosine kinase inhibitors (TKIs) such as imatinib or dasatinib are less effective in the treatment of Ph+ ALL. Integrins and focal adhesion kinase (FAK) are involved in the interaction between leukemic cells and their microenvironment, and contribute to leukemia cell resistance.
We hypothesized that by adding the targets of interfering through VLA-5 integrin and FAK, we can block the interaction between leukemia cells and their microenvironment and increase the treatment efficacy in Ph+ ALL in combination with TKIs.
Methods and Materials and Data Analysis
We will use cell based assays and leukemia mice model to test our hypothesis. We will also use RNA interference to knock down the targets we picked to see how they affect the in vitro and in vivo growth of the Ph+ ALL cells.
Role of Medical Student
Students can choose some procedures of the project, such as RNA knock down assay, cell based assay or animal part of the experiment.
Our project currently was funded by Dr Slayton’s department chief start funding. We are applying several outside funding.
Zhongbo Hu, Xiaomiao Li, David Ostrov, and William Slayton. Screening Small Molecule Inhibitors of VLA-5 to Block the Interaction Between Acute Lymphoblastic Leukemia with Ph+ and Their Microenvironment. 52nd ASH Annual Meeting, December 4-7 2010. Orlando, Florida
Zhongbo Hu, Xiao-Miao Li, Marda L. Jorgensen, William B. Slayton. MLL/AF-4 leukemic cells recruit new blood vessels but do not incorporate into capillaries in culture or in a NOD/SCID xenograft model. Leukemia, 2009; 23(5): 990-993.
The tumor microenvironment. Dietmar W. Siemann, Eds. Chapter 6. Bone Marrow Stroma and the Leukemic Microenvironment. William Slayton and Zhongbo Hu. New York, USA: Wiley Publications. October, 2010. ISBN: 978-0-470-66980-8