Effect of histone deacetylase inhibitor valproic acid on progenitor cells of acute myeloid leukemia.
Histone deacetylase inhibitor valproic acid (VPA) was recently shown to enhance proliferation and self-renewal of normal hematopoietic stem cells, raising the possibility that VPA may also support growth of leukemic progenitor cells (LPC). Here, VPA maintains a significantly higher proportion of CD34+ LPC and colony forming units compared to control cultures in six AML samples, but selectively reduces leukemic cell numbers in another AML sample with expression of AML1/ETO. Our data suggest a differential effect of VPA on the small population of AML progenitor cells and the bulk of aberrantly differentiated blasts in the majority of AML samples tested.
Bug
Gesine
G
Medizinische Klinik II, Abt. Hämatologie/Onkologie, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Theodor-Stern-Kai 7, Frankfurt, Germany. g.bug@em.uni-frankfurt.de
Schwarz
Kerstin
K
Schoch
Claudia
C
Kampfmann
Manuela
M
Henschler
Reinhard
R
Hoelzer
Dieter
D
Ottmann
Oliver G
OG
Ruthardt
Martin
M
D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000166:cytology / Q000187:drug effects; D002891:Chromosomes, Human, Pair 21 / Q000648:ultrastructure; D002898:Chromosomes, Human, Pair 8 / Q000648:ultrastructure; D050676:Core Binding Factor Alpha 2 Subunit / Q000032:analysis / Q000502:physiology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007951:Leukemia, Myeloid / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000187:drug effects*; D015514:Oncogene Proteins, Fusion / Q000032:analysis / Q000502:physiology; D000075142:RUNX1 Translocation Partner 1 Protein; D014178:Translocation, Genetic; D014410:Tumor Stem Cell Assay; D014635:Valproic Acid / Q000009:adverse effects* / Q000494:pharmacology
C107844:AML1-ETO fusion protein, human; D018952:Antigens, CD34; D050676:Core Binding Factor Alpha 2 Subunit; D056572:Histone Deacetylase Inhibitors; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein; D014635:Valproic Acid