Panobinostat inhibits the proliferation of CD34+ CD38- cells under stimulation of hematopoietic growth factors on AGM-S3 cells in juvenile myelomonocytic leukemia

Pediatric Blood & Cancer
Takashi KurataKenichi Koike

Abstract

Encouraging responses to histone deacetylase inhibitors have been reported for hematologic malignancies. Here, we report effects of panobinostat and 5-azacytidine on the proliferation of juvenile myelomonocytic leukemia (JMML) CD34+ cells. We previously reported that stimulation of JMML CD34+ cells with stem cell factor and thrombopoietin on irradiated murine AGM-S3 cells led to substantial expansion of JMML CD34+ cells that contained leukemic stem cells capable of transplantation into immunodeficient mice. Using this culture system, we evaluated effects of panobinostat and 5-azacytidine on the proliferation of JMML CD34+ cells. Panobinostat dose dependently reduced the numbers of day 7 CD34+ cells generated under stimulation of hematopoietic growth factors on AGM-S3 cells in all eight patients with JMML. These patients possessed various genetic and/or karyotypic abnormalities. CD34+ CD38- cells were substantially more sensitive to panobinostat at 10 and 20 nM than CD34+ CD38+ cells. Panobinostat, however, failed to influence the ability of AGM-S3 cells to stimulate JMML CD34+ cell production. In contrast to HL60 cells, apoptosis and cell cycle arrest in panobinostat-mediated inhibition were at low levels in JMML. The inhibitor...Continue Reading

References

Dec 8, 2000·The Oncologist·S HirschfeldR Pazdur
Mar 10, 2005·British Journal of Haematology·Daisuke HasegawaTatsutoshi Nakahata
Mar 3, 2006·Cancer Research·Carlo StresemannFrank Lyko
Mar 17, 2011·Blood·Christiane Olk-BatzUNKNOWN European Working Group of Myelodysplastic Syndromes in Childhood (EWOG-MDS)
May 16, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Guillermo Garcia-ManeroHagop M Kantarjian
Oct 23, 2012·Experimental Hematology·Takayuki TsujiokaKaoru Tohyama
May 6, 2015·European Journal of Clinical Pharmacology·Marina SavelievaRenaud Capdeville
Oct 13, 2015·Nature Genetics·Elliot StieglitzMignon L Loh
Feb 19, 2016·Epigenetics : Official Journal of the DNA Methylation Society·Thomas WilhelmChristoph Plass

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