Day 1 :
University of California, Los Angeles, USA
Time : 10:00-10:30
Robert H. Schiestl has obtained his PhD from the University of Vienna at the age of 23 years. He was postdoctoral fellow at Edmonton, Alberta, Rochester, NY, and Chapel Hill, NC before being professor at Harvard at the age of 31 where he stayed for 10 years. Since 15 years he is professor at UCLA with 187 publications, 10 patents and 2 startup companies.
Hematopoietic stem cell transplantation (HSCT) is often the only/last treatment option of some malignancies, congenital diseases and bone marrow failure. For efficient engraftment of donor HSC’s stem cell niches have to be provided. Here we developed an in vivo selection scheme for HSCT based on the fact that 6-thioguanine (6TG) toxicity is essentially predicated on its HPRT mediated conversion to thioguanine nucleotide and strongly myelosuppressive. At appropriate concentrations 6TG is strongly myeloablative with little toxicity to other tissues. Therefore it is possible to eliminate diseased bone marrow and replace it with healthy donor bone marrow that lacks HPRT.rnWe have shown that only Hprt proficient cells are susceptible to 6-TG allowing selection in favor of Hprt deficient donor HSC’s in vivo and that a 4 week selection regimen results in a 95% replacement of the hosts marrow. Engraftment is more robust with 6-TG selection than with radiation. The proposed method offers selection through a less toxic compound (compared to other schemes) hence less side effects, use of smaller, siRNA-producing vectors (therefore potentially more efficient), possible use of non-integrating vectors and less patient discomfort.rnThe general aim of this project is to show that HSC’s deficient for HPRT can be selected for in vivo through 6TG administration, that this procedure would be applicable for conditions like hematological malignancies, congenital diseases and bone marrow failure i.e. where HSCT is indicated and to test all aspects of this procedure to eventually allow for phase I clinical trials.rn
The University of Texas, USA
Time : 10:30-11:00
C Cameron Yin has received her MD from Beijing Medical University and her PhD from the University of Wisconsin-Madison. She is currently an Associate Professor in the Department of Hematopathology at the University of Texas MD Anderson Cancer Center. In addition to clinical responsibilities on the Leukemia, Lymphoma and Molecular Diagnostic services, she has been actively participating in multiple research projects in the molecular genetic abnormalities in leukemia and lymphoma, which has led to over 100 research papers and over 20 book chapters.
We studied immunoglobulin gamma heavy chain (IgG) expression in acute myeloid leukemia (AML) and found that IgG was expressed at a high frequency and level in AML cell lines and primary myeloblasts but not in monocytes or neutrophils from patients with non-hematopoietic neoplasms or healthy controls. We further detected IgG VHDJH transcripts in AML cell lines and sorted primary myeloblasts, confirming that IgG expression was indeed produced by AML cells. AML-IgG gene rearrangements showed evidence of somatic hyper mutation and restricted (AML cell lines) or biased (primary myeloblasts) V usage. Anti-human IgG reduced cell viability and induced apoptosis in AML cell lines. Our findings suggest that AML-IgG may play a role in leukemogenesis and AML progression. AML-IgG may serve as a useful molecular marker for monitoring minimal residual disease or designing target therapy.