Stem cell factor and PIXY-321 in acute lymphoblastic leukemia: in vitro study on proliferative effects and apoptosis.
Cytokines Mol Ther
; 2(4): 225-30, 1996 Dec.
Article
em En
| MEDLINE
| ID: mdl-9384708
ABSTRACT
Management of acute lymphoblastic leukemia (ALL) patients may include growth factors (GFs) to reduce post-chemotherapy aplasia. A potential risk of GF administration is a stimulatory signal on the leukemic population. In the present study we investigated the proliferative and programmed cell death (PCD) effect of two cytokines that have recently entered clinical use, stem cell factor (SCF) and the granulocyte colony stimulating factor/IL-3 fusion molecule (PIXY-321), on 14 ALL samples. The activity of IL-7, a cytokine involved in the regulation of ALL cell proliferation, was also tested alone and in combination with these two cytokines. Using the acridine orange flow cytometric technique and the clonogenic assay, we showed that none of these cytokines was capable of significantly increasing the mean percentage of S-phase cells and CFU-L number. A mean decrease of G0 cells from 60.6% to 52.6% (p = 0.02), coupled by a significant increase of G1 cells from 28.2% to 37.9% (p = 0.003) was demonstrated in the presence of PIXY-321. IL-7 alone and in combination with either PIXY-321 or SCF induced similar changes in the percentage of cells in G0 and G1. SCF showed no activity on G0 depletion. When each individual samples was analyzed separately, some heterogeneity was observed. An increase of S phase was recorded in a proportion of cases after SCF and PIXY-321 exposure. However, none of the cytokines evaluated by a clonogenic assay following liquid culture was capable of maintaining or promoting self-renewal of leukemic precursors, as determined by plating fresh cells at time 0. Detection of cytokine effects of apoptosis showed that SCF and PIXY-321 did not significantly reduce the mean percentage of cells in PCD, whereas a significant protective effect was observed in the presence of IL-7 (p = 0.02). We conclude that PIXY-321 and, to a further extent, SCF fail to induce leukemic lymphoid cell proliferation, and do not protect cells from entering apoptosis. These in vitro findings may be useful for ALL clinical trial design.
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Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
/
6_ODS3_enfermedades_notrasmisibles
/
7_ODS3_muertes_prevenibles_nacidos_ninos
Base de dados:
MEDLINE
Assunto principal:
Células da Medula Óssea
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Células-Tronco Hematopoéticas
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Ciclo Celular
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Fator Estimulador de Colônias de Granulócitos e Macrófagos
/
Interleucina-7
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Interleucina-3
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Fator de Células-Tronco
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Leucemia-Linfoma Linfoblástico de Células Precursoras
Limite:
Adolescent
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Adult
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Child
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Child, preschool
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Humans
Idioma:
En
Revista:
Cytokines Mol Ther
Ano de publicação:
1996
Tipo de documento:
Article