Acute myelogenous leukemia (AML) is often a fatal disease where after strong induction
therapy most patients relapse and die [1, 2]. A-type proanthocyanidins (A-PACs) are
a unique class of compounds found in cranberries (Vaccinium macrocarpon Ait.) that we have found to be effective against several leukemia cell lines and
primary AML samples in vitro. An A-PAC fraction, isolated from the cranberry powder CystiCran®40 (Naturex; Avignon, France), was found to selectively ablate leukemia stem and progenitor
cells, with minimal effects on normal hematopoetic stem cells. Furthermore, AML engraftment
of cells treated ex vivo with 62.5 µg/ml A-PACs was decreased compared to controls
(90.6%, n = 3, P < 0.001), whereas normal CD34+ cells retained engraftment capability
in immunodeficient mice. Administration of A-PACs to AML-patient derived xenotransplants
(PDX) significantly reduced tumor burden in mice. Specifically, mice treated with
50 mg/kg and 25 mg/kg of A-PACs exhibited a 56.8% (n = 5) and 58.4% (n = 5) reduction
in tumor burden, respectively, compared to the mice treated with the vehicle control
(P < 0.05). These effects were better or equal to those observed in mice treated with
high-dose cytarabine, a standard care drug. Moreover, no toxic effects were observed
in the mice. These results indicate that A-PACs not only target primary AML cells
in vitro, but are also effective in vivo by potentially a novel mechanism that may also target
stem cells. Further elucidation of this mechanism may uncover new vulnerabilities
of AML.
Acknowledgements: L.M. Bystrom was funded by NCCIH (award number F32AT007112) and
M.L. Guzman was funded by the NIH Director's New Innovator Award Program (1 DP2 OD007399
– 01).
Keywords: Cranberry, leukemia, proanthocyanidins, xenotransplants.
References:
[1] Burnett A, Wetzler M, Lowenberg B. Therapeutic advances in acute myeloid leukemia. J Clin Oncol 2011; 29: 487 – 494
[2] Lowenberg B, Downing JR, Burnett A. Acute myeloid leukemia. N Engl J Med 1999; 341: 1051 – 1062
