PPTP Acute Lymphoblastic Leukemia Xenograft Testing Laboratory

Lab Website: http://www.ccia.org.au/page.php?id=96

Director: Richard Lock, PhD

This laboratory employs multiple xenograft models of human acute lymphoblastic leukemia (ALL) that have been directly established in nod/SCID mice. These xenografts have been established from patients with relapse/refractory ALL and also from patients who had responsive disease.

ALL cells are injected into mice via the tail vein and engraftment of the ALL cells determined by monitoring circulating ALL cells in the blood using flow cytometry and anti- human CD45 (1, 2).

Clinical Trials Enabled by this Laboratory

Data generated by the PPTP screen showing activity of bortezomib in the ALL xenografts confirmed data obtained in vitro by other investigators and helped enable the ongoing TACL phase I study of bortezomib + vincristine, dexamethasone, and L-aspariginase (T2005-003).

Laboratory Funding

NCI PPTP Grant

Laboratory Publications

1. Bachmann, PS, Gorman, R, MacKenzie, KL, Lutze-Mann, L, and Lock, RB Dexamethasone resistance in B-cell precursor childhood acute lymphoblastic leukemia occurs downstream of ligand-induced nuclear translocation of the glucocorticoid receptor. Blood 105(6):2519-26, 2005.
2. Bendall, LJ, Nilsson, SK, Khan, NI, James, A, Bonnet, C, Lock, RB, Papa, R, Bradstock, KF, and Gottlieb, DJ Role of CD44 variant exon 6 in acute lymphoblastic leukaemia: association with altered bone marrow localisation and increased tumor burden. Leukemia, 18: 1308-1319, 2004.
3. Liem, NLM, Papa, RA, Milross, CG, Schmid, MA, Tajbakhsh, M, Choi, S, Ramirez, CD, Rice, AM, Haber, M, Norris, MD, MacKenzie, KL, and Lock, RB Characterization of childhood acute lymphoblastic leukemia xenograft models for the preclinical evaluation of new therapies. Blood, 103: 3905-3914, 2004.
4. Lock, RB TCL1: a new drug target in lymphoid and germ-cell malignancies? Int J Biochem Cell Biol, 35: 1614-1618. 2003
5. Houghton, P.J., Adamson, P.C., Blaney, S., Fine, H.A., Gorlick, R., Haber, M., Helman, L., Hirschfeld, S., Hollingshead, M.G., Israel, M.A., Lock, R.B., Maris, J.M., Merlino, G. Patterson, W., Reynolds, C.P., Shannon, K., Yu, A., Yu, J., Smith, M.A. (2002). Testing of new agents in childhood cancer preclinical models : meeting summary. Clin Cancer Res. 8: 3646-3657.

Bibliography

1. Liem, NLM, Papa, RA, Milross, CG, Schmid, MA, Tajbakhsh, M, Choi, S, Ramirez, CD, Rice, AM, Haber, M, Norris, MD, MacKenzie, KL, and Lock, RB Characterization of childhood acute lymphoblastic leukemia xenograft models for the preclinical evaluation of new therapies. Blood, 103: 3905-3914, 2004.
2. Look RB, Liem NL, Papa RA:Preclinical testing of antileukemic drugs using an in vivo model of systemic disease Methods Mol Med. ;111:323-34, 2005.