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

Abstract

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.

Transcriptional regulation of the cyclin D1 promoter by STAT5: its involvement in cytokine-dependent growth of hematopoietic cells

“…Cells and cell culture F-36P, a human IL-3-dependent erythroleukemia cell line originally established by Chiba et al (1991) was obtained from Riken Cell Bank (Tsukuba, Japan). Several stable transformants from F-36P cells were cultured in RPMI 1640 (Nakarai Tesque, Kyoto, Japan) supplemented with 10% fetal calf serum (FCS; Flow, North Ryde, Australia) in the presence of 5 ng/ml rhIL-3.…”

Immunophenotypic, cytogenetic, and mutational characterization of cell lines derived from myelodysplastic syndrome patients after progression to acute myeloid leukemia

“…Enforced differentiation is a valid approach in leukemia therapy, which is best exemplified by the success of all trans retinoic acid in the treatment of acute promyelocytic leukemia (Nowak et al, 2009). The MDS/AML cell lines MOLM-13 and F-36P retain a partial capacity to differentiate into the erythroid and monocytic lineage, respectively (Chiba et al, 1991;Matsuo et al, 1997;Thompson et al, 2010), making them useful tools to test differentiation promoting drugs.…”

“…Here, we have used a large panel of flow cytometric markers and whole genome single nucleotide polymorphism (SNP) arrays to improve the immunophenotypic characterization and to redefine the cytogenetic features of four MDS/AML cell lines. These include the cell lines MOLM-13 (Matsuo et al, 1997), SKM-1 (Nakagawa et al, 1993), F-36P (Chiba et al, 1991), and the less characterized SKK-1 cell line (Matsuoka et al, 2005). We further provide a detailed cytogenetic profile of the OHN-GM cell line (Nagai et al, 1997) which contains del(5q) in the context of a complex karyotype.…”

Engraftment of human myelodysplastic syndrome derived cell line in transgenic severe combined immunodeficient (TG‐SCID) mice expressing human GM–CSF and IL‐3

“…Preparation and Introduction of the human myeloid cell line, F-36P. into mice F-36P, a myeloid leukemia cell line from a patient with myelodysplastic syndrome (26), was maintained in RPMI 1640 medium (GIBCO-BRL, Burlington, USA) supplemented with 10% FCS in the presence of 10 ng/ml of the human cytokines GM-CSF or IL-3. Cells were cultured in tissue culture flasks at 37°C in a humidified 5% CO, atmosphere.…”