Effect of myelopoietic and pleiotropic cytokines on colony formation by blast cells of children with acute lymphoblastic leukemia.
The aim of this study was to see whether pleiotropic or myeloid hematopoietic growth factors, which do not stimulate normal lymphoid cells, can induce proliferation of blast cells of the acute lymphoid leukemia (ALL) of childhood. Bone marrow cells of 13 children with untreated ALL (nine common ALL, two myeloid antigen positive ALL and two early T-cell ALL) formed colonies of leukemic blast cells in primary methylcellulose cultures. Spontaneous growth was observed in three of 13 cases, whereas phytohemagglutinin-stimulated leukocyte conditioned medium (PHA-LCM), a conventional source of various natural human cytokines, induced colony formation in ten of 13 cases. A similar rate of responsiveness was seen with recombinant human granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF) and stem cell factor (SCF); a combination of these three cytokines induced colony formation in all cases studied. The effect of these growth factors on colony formation seemed to be dose-dependent in some cases. Of the stimuli studied, GM-CSF induced the smallest number of colonies, whereas the effects of G-CSF, SCF and PHA-LCM were similar in this respect. Combination of cytokines proved to be even more efficient in inducing clonal proliferation of leukemic lymphoblasts. In double combinations, G-CSF and GM-CSF as well as G-CSF and SCF were able to potentiate each other's effects. Triple combination of these cytokines mediated the most potent growth stimulus. Our results demonstrate that myeloid and pleiotropic cytokines are able to stimulate clonal proliferation of pediatric leukemic lymphoblasts. This may present a potential hazard to children with ALL while on adjuvant therapy with hematopoietic growth factors. In vitro colony assays performed prior to or in parallel with the administration of hematopoietic growth factors to ALL patients may help to forecast their possible effects on leukemic cells in vivo.
Benko
I
I
Department of Pharmacology, Medical School, Medical and Health Science Center, University of Debrecen, Hungary. benko@king.pharmacol.dote.hu
Kovács
P
P
Szegedi
I
I
Megyeri
A
A
Kiss
A
A
Balogh
E
E
Oláh
E
E
Kappelmayer
J
J
Kiss
C
C
D000293:Adolescent; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins / Q000494:pharmacology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006801:Humans; D007223:Infant; D007377:Interleukin-3; D008297:Male; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism / Q000473:pathology*; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D014410:Tumor Stem Cell Assay
D002352:Carrier Proteins; D016207:Cytokines; D006133:Growth Substances; D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C404145:myelopoietin; C066845:pleiotrophin; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor