Effect of vesnarinone, a quinolinone derivative, on the growth of leukemic blasts in acute myelogenous leukemia.
We studied the effects of vesnarinone, a quinolinone derivative used clinically for the treatment of chronic congestive heart failure, on the leukemic blast progenitors in acute myelogenous leukemia (AML) patients and on the normal hematopoietic precursors, colony-forming unit in culture (CFU-C), and colony-forming unit erythroid (CFU-E). Leukemic blast progenitors made blast colonies in the presence of granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), or interleukin-3 (IL-3). Blast colony-formation was suppressed by vesnarinone in a dose-responsive manner regardless of growth factor added. Vesnarinone suppressed the primary (PE1) and secondary (PE2) colony-formation of leukemic blast progenitors in six AML patients tested. The suppression by vesnarinone did not significantly differ between PE1 and PE2. This finding suggests that vesnarinone exerts an almost equivalent effects on the terminal divisions and the self-renewal of leukemic blast progenitors. Furthermore, this drug suppressed the growth of clonogenic cells of five AML cell lines, OCI/AML1a, OCI/AML2, OCI/AML3, OCI/AML5, and OCI/AML6. Normal hematopoietic precursors CFU-C and CFU-E were also suppressed by vesnarinone, although vesnarinone was less toxic to normal hematopoietic than to leukemic blast progenitors. The possible usefulness of vesnarinone as a new approach to the treatment of AML patients is discussed.
Nara
N
N
Department of Laboratory Medicine, Faculty of Medicine, Tokyo Medical and Dental University, Japan.
Kurokawa
H
H
Tohda
S
S
Tomiyama
J
J
Nagata
K
K
Tanikawa
S
S
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003114:Colony-Forming Units Assay; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011719:Pyrazines; D011804:Quinolines / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D011719:Pyrazines; D011804:Quinolines; C041667:vesnarinone