Bone Marrow and Peripheral Blood AML Cells Are Highly Sensitive to CNDAC, the Active Form of Sapacitabine
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...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Advances in Hematology |
| Online Access: | http://dx.doi.org/10.1155/2012/727683 |
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| author | Sucheta Jagan Laura A. Paganessi Robin R. Frank Parameswaran Venugopal Melissa Larson Kent W. Christopherson |
| author_facet | Sucheta Jagan Laura A. Paganessi Robin R. Frank Parameswaran Venugopal Melissa Larson Kent W. Christopherson |
| author_sort | Sucheta Jagan |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d7ebb082ebff4ad2b97b3a26362a4257 |
| institution | OA Journals |
| issn | 1687-9104 1687-9112 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advances in Hematology |
| spelling | doaj-art-d7ebb082ebff4ad2b97b3a26362a42572025-08-20T02:21:25ZengWileyAdvances in Hematology1687-91041687-91122012-01-01201210.1155/2012/727683727683Bone Marrow and Peripheral Blood AML Cells Are Highly Sensitive to CNDAC, the Active Form of SapacitabineSucheta Jagan0Laura A. Paganessi1Robin R. Frank2Parameswaran Venugopal3Melissa Larson4Kent W. Christopherson5Section of Bone Marrow Transplant and Cell Therapy, Rush University Medical Center, 1725 West Harrison Street, Chicago, IL 60612, USASection of Bone Marrow Transplant and Cell Therapy, Rush University Medical Center, 1725 West Harrison Street, Chicago, IL 60612, USASection of Bone Marrow Transplant and Cell Therapy, Rush University Medical Center, 1725 West Harrison Street, Chicago, IL 60612, USARush University Cancer Center, 1725 West Harrison Street, Chicago, IL 60612, USARush University Cancer Center, 1725 West Harrison Street, Chicago, IL 60612, USASection of Bone Marrow Transplant and Cell Therapy, Rush University Medical Center, 1725 West Harrison Street, Chicago, IL 60612, USAAchieving 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.http://dx.doi.org/10.1155/2012/727683 |
| spellingShingle | Sucheta Jagan Laura A. Paganessi Robin R. Frank Parameswaran Venugopal Melissa Larson Kent W. Christopherson Bone Marrow and Peripheral Blood AML Cells Are Highly Sensitive to CNDAC, the Active Form of Sapacitabine Advances in Hematology |
| title | Bone Marrow and Peripheral Blood AML Cells Are Highly Sensitive to CNDAC, the Active Form of Sapacitabine |
| title_full | Bone Marrow and Peripheral Blood AML Cells Are Highly Sensitive to CNDAC, the Active Form of Sapacitabine |
| title_fullStr | Bone Marrow and Peripheral Blood AML Cells Are Highly Sensitive to CNDAC, the Active Form of Sapacitabine |
| title_full_unstemmed | Bone Marrow and Peripheral Blood AML Cells Are Highly Sensitive to CNDAC, the Active Form of Sapacitabine |
| title_short | Bone Marrow and Peripheral Blood AML Cells Are Highly Sensitive to CNDAC, the Active Form of Sapacitabine |
| title_sort | bone marrow and peripheral blood aml cells are highly sensitive to cndac the active form of sapacitabine |
| url | http://dx.doi.org/10.1155/2012/727683 |
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