Abstract |
Several neplanocin A analogs were synthesized and their growth-inhibiting and differentiation-inducing activities on myelogenous leukemia cells were examined. An adenosine kinase-ineffective analog of neplanocin A was effective in inducing differentiation, suggesting that phosphorylation of the nucleoside is not essential for inducing the differentiation of leukemia cells. Neplanocin A induced functional and morphological differentiation of HL-60 cells, but did not effectively induce differentiation of NB4, a cell line derived from a leukemia patient with t(15;17). However, these cells have been known to undergo granulocytic differentiation upon treatment with all-trans retinoic acid (ATRA), and are used as a model for differentiation therapy in acute promyelocytic leukemia. Preexposure of NB4 cells to low concentrations of neplanocin A greatly enhanced the ATRA-induced differentiation of the cells, whereas representative antileukemic drugs such as cytosine arabinoside and daunomycin did not enhance this differentiation. A clinical strategy that combines intermittent treatment with neplanocin A analogs and a low dose of ATRA may increase the clinical response and decrease the adverse effects of ATRA.
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Authors | N Niitsu, Y Yamamoto-Yamaguchi, Y Kanatani, S Shuto, A Matsuda, M Umeda, Y Honma |
Journal | Experimental hematology
(Exp Hematol)
Vol. 25
Issue 12
Pg. 1296-303
(Nov 1997)
ISSN: 0301-472X [Print] Netherlands |
PMID | 9357974
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibiotics, Antineoplastic
- Antineoplastic Agents
- DNA, Neoplasm
- Enzyme Inhibitors
- Cytarabine
- Tretinoin
- neplanocin A
- Hydrolases
- Adenosylhomocysteinase
- Adenosine
- Daunorubicin
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Topics |
- Adenosine
(administration & dosage, analogs & derivatives)
- Adenosylhomocysteinase
- Antibiotics, Antineoplastic
(pharmacology)
- Antineoplastic Agents
(pharmacology)
- Cell Cycle
(drug effects)
- Cell Differentiation
(drug effects)
- Cytarabine
(pharmacology)
- DNA, Neoplasm
(analysis)
- Daunorubicin
(administration & dosage)
- Drug Synergism
- Enzyme Inhibitors
(pharmacology)
- Granulocytes
(cytology)
- Humans
- Hydrolases
(antagonists & inhibitors)
- Leukemia, Promyelocytic, Acute
(pathology)
- Leukopoiesis
(drug effects)
- Tretinoin
(administration & dosage)
- Tumor Cells, Cultured
(drug effects)
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