Self-renewal inhibition of acute myeloid leukemia clonogenic cells by biological inducers of differentiation

Dario Ferrero, Nadia Carlesso, Patrizia Pregno, Eugenio Gallo, Alessandro Pileri

Research output: Contribution to journalArticle

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Abstract

We analyzed the maintenance of acute myeloid leukemia clonogenic cells (AML CFU-L) in liquid culture in the presence of five potential differentiation inducers: trans-retinoic acid, 1,25-dihydroxy vitamin D3, Interferon γ, granulocyte colonystimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), used singly and with two combined. The culture medium contained either fetal bovine or human serum from normal donors. CFU-L recovery after 7 days was compared to that observed in control cultures. Of AML cases and HL60 cells, 11/15 displayed > 50% CFU-L reduction in response to one or more inducers. In 8/9 responsive cases that underwent the nitroblue tetrazolium (NBT) reduction test, an increase in the percentage of functionally mature (NBT-positive) cells was detected. The combination of retinoic acid with Interferon γwas most effective in reducing CFU-L recovering (8 responsive/15 AML cases), G-CSF and M-CSF displayed either inhibitory or stimulatory activity in different AML cases. The type of serum employed generally did not affect the response to inducers of differentiation. No significant inhibition of the recovery of granulocyte-macrophage colony-forming units was determined by the five inducers in experiments with three normal bone marrow samples. Our experiments indicate that biological differentiation inducers can reduce AML CFU-L self-renewal and increase the proportion of differentiated cells at concentra-tions that do not affect normal myelopoiesis and could be achieved during treatments in vivo.

Original languageEnglish (US)
Pages (from-to)100-106
Number of pages7
JournalLeukemia
Volume6
Issue number2
StatePublished - Feb 1992
Externally publishedYes

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Helper-Inducer T-Lymphocytes
Acute Myeloid Leukemia
Nitroblue Tetrazolium
Macrophage Colony-Stimulating Factor
Tretinoin
Granulocytes
Interferons
Myelopoiesis
Granulocyte-Macrophage Progenitor Cells
HL-60 Cells
Serum
Culture Media
Bone Marrow
Maintenance

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

Self-renewal inhibition of acute myeloid leukemia clonogenic cells by biological inducers of differentiation. / Ferrero, Dario; Carlesso, Nadia; Pregno, Patrizia; Gallo, Eugenio; Pileri, Alessandro.

In: Leukemia, Vol. 6, No. 2, 02.1992, p. 100-106.

Research output: Contribution to journalArticle

Ferrero, Dario ; Carlesso, Nadia ; Pregno, Patrizia ; Gallo, Eugenio ; Pileri, Alessandro. / Self-renewal inhibition of acute myeloid leukemia clonogenic cells by biological inducers of differentiation. In: Leukemia. 1992 ; Vol. 6, No. 2. pp. 100-106.
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