Interleukin-4 as a growth regulator of clonogenic cells in acute myelogenous leukemia in suspension culture.
Using two complementary culture systems, suspension and clonal cultures, and with a method of graphic display (star diagram), we studied the effects of recombinant human interleukin-4 (IL-4) on leukemic stem cell renewal and differentiation in acute myelogenous leukemia (AML). The interactions between IL-4 and other recombinant human cytokines, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), macrophage CSF (M-CSF) and interleukins-1 alpha, -2, -3, -5, and -6 were also studied. IL-4 alone had significant effects on both self-renewal and differentiation of blast progenitors in some cases; in clonogenic assay, IL-4 stimulated blast colony formation and in one case IL-4 was the most powerful stimulator among the nine growth factors tested. Star diagrams, constructed using the data from both suspension and clonal cultures, showed that IL-4 could influence the balance between self-renewal and differentiation of clonogenic cells. Negative and positive interactions were detected between IL-4 and other cytokines in suspension culture. These results indicate that IL-4 is a cytokine with a potential role in regulating the growth of myeloid leukemic stem cells, and that IL-4 may be useful in treating selected AML patients.
Miyauchi
J
J
Central Laboratory, National Children's Hospital, Tokyo, Japan.
Clark
S C
SC
Tsunematsu
Y
Y
Shimizu
K
K
Park
J W
JW
Ogawa
T
T
Toyama
K
K
D000328:Adult; D000368:Aged; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000503:physiopathology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000494:pharmacology
D007375:Interleukin-1; D007376:Interleukin-2; D007377:Interleukin-3; D015848:Interleukin-5; D015850:Interleukin-6; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D015847:Interleukin-4; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor