1. A phase 1 and pharmacodynamic study of depsipeptide (FK228) in chronic lymphocytic leukemia and acute myeloid leukemia
by John C. Byrd, Guido Marcucci, Mark R. Parthun, Jim J. Xiao, Rebecca B. Klisovic, Mollie Moran, Thomas S. Lin, Shujun Liu, Amy R. Sklenar, Melanie E. Davis, David M. Lucas, Beth Fischer, Roshini Shank, Sooraj L. Tejaswi, Philip Binkley, John Wright, Kenneth K. Chan, and Michael R. Grever
Blood
Volume 105(3):
February 1, 2005
©2005 by American Society of Hematology

2. Biologic effects of depsipeptide in CLL patient cells.
Biologic effects of depsipeptide in CLL patient cells. (A) CLL patient cells were isolated prior to therapy with depsipeptide, as well as immediately before treatment and 4 and 24 hours after the start of infusion. Lysates were prepared and analyzed for specific HDAC activity. Activity is shown as a percentage relative to baseline (pretreatment). Significant HDAC inhibition is noted at completion of infusion (4 hours) and diminishes by 24 hours. (B) CLL patient cells isolated before therapy and at 4 hours following the start of the infusion were analyzed by fluorescent immunocytochemistry using an antibody to acetylated H3. Acetylation of H3 is minimal at baseline but is evident in the majority of the cells at the 4-hour time point.
John C. Byrd et al. Blood 2005;105:
©2005 by American Society of Hematology

3. Effects of depsipeptide on p21 in vivo.
Effects of depsipeptide on p21 in vivo. (A) Lysates from CLL patient cells obtained before and 4 or 24 hours after depsipeptide administration were analyzed by immunoblot using an anti-p21 antibody. Simultaneous incubation with anti-GAPDH antibody was performed to detect protein-loading differences. (B) Cells from these same time points were subjected to chromatin immunoprecipitation analysis using anti-acetylated H4 antibody. The graph shows the increase in p21 promoter acetylation relative to GAPDH.
John C. Byrd et al. Blood 2005;105:
©2005 by American Society of Hematology

4. Depsipeptide causes increased 1D10 antigen expression in vivo.
Depsipeptide causes increased 1D10 antigen expression in vivo. Before and 24 hours following treatment with 13 mg/m2 depsipeptide of a patient with CLL, peripheral mononuclear cells were isolated and analyzed simultaneously for surface expression of CD19 and the HLA-DR antigen 1D10.
John C. Byrd et al. Blood 2005;105:
©2005 by American Society of Hematology