Effects of mast cell growth factor on Ara-C mediated acute myeloid leukemia cell killing.
Cell kinetic studies of acute myeloid leukemia (AML) have provided evidence for the presence of nonproliferating cells. Hemopoietic growth factors (GF) can regulate proliferation of leukemic cells, furnishing new possibilities for recruiting quiescent cells into the cycle and overcoming cytokinetic resistance in AML. To assess the role of the novel identified cytokine, mast cell growth factor (MGF), in enhancing cytosine arabinoside (Ara-C) cytotoxicity, we have primed AML blasts with MGF and then exposed these cells to the S phase specific agent Ara-C. Other growth factors such as PIXY, interleukin 3 (IL-3), granulocyte-macrophage colony stimulating factor (GM-CSF) and granulocyte CSF (G-CSF) and the combination of MGF plus PIXY were also tested. Cytokinetic changes and clonogenic growth of leukemic colony forming unit (CFU-L) cells in methylcellulose were used to detect proliferative and cytotoxic effects on AML blasts. Expression of MGF receptor, the c-kit protein, was also measured by flow cytometry. We report in this preliminary study that MGF is able to increase proliferation in 75% of the samples studied and enhance Ara-C cytotoxicity in some of these cases. When MGF proliferative activity was compared with other GFs, individual cases showed heterogeneity in response, although the combination of MGF plus PIXY was always the most effective.
Tafuri
A
A
Department of Biopathology, University La Sapienza of Rome, Italy.
De Felice
L
L
Mascolo
M G
MG
Valentini
T
T
Petrucci
M T
MT
Petti
M C
MC
D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death; D002455:Cell Division / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology*; D004357:Drug Synergism; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D009363:Neoplasm Proteins / Q000032:analysis; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis; D016184:Receptors, Colony-Stimulating Factor / Q000032:analysis; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014410:Tumor Stem Cell Assay
D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D016184:Receptors, Colony-Stimulating Factor; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases