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Advances in Hematology
Volume 2012 (2012), Article ID 727683, 12 pages
http://dx.doi.org/10.1155/2012/727683
Research Article

Bone Marrow and Peripheral Blood AML Cells Are Highly Sensitive to CNDAC, the Active Form of Sapacitabine

1Section of Bone Marrow Transplant and Cell Therapy, Rush University Medical Center, 1725 West Harrison Street, Chicago, IL 60612, USA
2Rush University Cancer Center, 1725 West Harrison Street, Chicago, IL 60612, USA
3Section of Hematology, Rush University Medical Center, 1725 West Harrison Street, Chicago, IL 60612, USA
4Department of Anatomy and Cell Biology, Rush University Medical Center, 1725 West Harrison Street, Chicago, IL 60612, USA

Received 18 June 2012; Accepted 4 August 2012

Academic Editor: Seiji Fukuda

Copyright © 2012 Sucheta Jagan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Achieving improvements in survival and reducing relapse remains a challenge in acute myelogenous leukemia (AML) patients. This study evaluated the in vitro efficacy of the active form of novel agent sapacitabine, CNDAC, compared to current chemotherapeutic drugs Ara-C and mitoxantrone using two AML cell lines, HL-60 (promyelocytic) and THP-1 (monocytic), as well as bone marrow (BM) and peripheral blood (PB) cells collected from AML patients. Cell lines were exposed to compound for 3–6 days and primary cells for 4 days. The viability of primary cells was additionally evaluated 3, 7, and 31 days after removal of tested compound to determine the durability of the response. Our studies indicate that CNDAC and mitoxantrone have a greater impact on viability than ara-C in primary AML cells and AML cell lines. CNDAC is more effective at reducing viability and inducing apoptosis than ara-C at equivalent concentrations in the THP-1 cell line, which is defined as displaying resistance to ara-C. As sapacitabine has shown in vivo activity at clinically achievable doses, future studies are warranted to assess the potential for combining it with ara-C and/or mitoxantrone, with an emphasis on cells and patients insensitive to ara-C treatment.