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.
Highlights
Acute myeloid leukemia (AML) therapy is continually challenged by high incidences of disease relapse and patient mortality
This study evaluated the in vitro efficacy of the active form of novel agent sapacitabine, Cyano2 -deoxy-1-β-d-arabino-pentofuranosylcytosine (CNDAC), compared to current chemotherapeutic drugs Ara-C and mitoxantrone using two acute myelogenous leukemia (AML) cell lines, HL-60 and THP-1, as well as bone marrow (BM) and peripheral blood (PB) cells collected from AML patients
Our studies indicate that CNDAC and mitoxantrone have a greater impact on viability than ara-C in primary AML cells and AML cell lines
Summary
Acute myeloid leukemia (AML) therapy is continually challenged by high incidences of disease relapse and patient mortality. The overall 5-year survival rate for AML is 30– 40% for patients >45 years and
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