Establishment and erythroid differentiation of a cytokine-dependent human leukemic cell line F-36: a parental line requiring granulocyte-macrophage colony-stimulating factor or interleukin-3, and a subline requiring erythropoietin.
We have established a new nonlymphoid leukemic cell ine from a patient with myelodysplastic syndrome (MDS), which progressed to overt leukemia. The parental cell line and a subline derived from this line have absolute dependency on several cytokines for their long-term survival and growth. The parental line designated F-36P requires granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3) for continuous growth, while a subline designated F-36E can be maintained in the presence of erythropoietin (Epo) alone. When these cytokines are depleted, both the parental and the subline cells die within several days, even in medium supplemented with fetal calf serum (FCS). F-36E, maintained in the presence of Epo, constitutively synthesizes hemoglobin at a significant level. F-36P, which is usually maintained in the presence of GM-CSF or IL-3, can be induced to synthesize hemoglobin when GM-CSF or IL-3 is substituted by Epo. The surface marker profile shows that the F-36P cells are positive for the leukocyte common antigen (CD45) and some common multilineage markers such as CD13, CD33, and CD34, and negative for T- and B-cell antigens and mature myelomonocytic antigens. However, some monoclonal antibodies recognizing erythroid and platelet glycoproteins react with these cells. Thus, this cell line has a multilineage phenotype, suggesting that the transformation event occurred in a multipotent stem cell. It is also evident that the F-36 cells can be induced to differentiate into the erythroid lineage in the presence of Epo. This, to our knowledge, is the first description of a human leukemic cell line that can be stimulated to synthesize hemoglobin by Epo.
Chiba
S
S
Third Department of Internal Medicine, University of Tokyo, Japan.
Takaku
F
F
Tange
T
T
Shibuya
K
K
Misawa
C
C
Sasaki
K
K
Miyagawa
K
K
Yazaki
Y
Y
Hirai
H
H
D000954:Antigens, Surface / Q000032:analysis; D002454:Cell Differentiation; D002455:Cell Division; D002470:Cell Survival; D004912:Erythrocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D004921:Erythropoietin / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006454:Hemoglobins / Q000096:biosynthesis; D006651:Histocytochemistry; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D007621:Karyotyping; D007938:Leukemia / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008854:Microscopy, Electron; D009190:Myelodysplastic Syndromes / Q000473:pathology; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000954:Antigens, Surface; D006454:Hemoglobins; D007377:Interleukin-3; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D004921:Erythropoietin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor