Establishment and characterization of a new human leukemia cell line derived from M4E0

Abstract

A new human leukemia cell line, designated as ME-1, was established from the peripheral blood leukemia cells of a patient with acute myelomonocytic leukemia with eosinophilia (M4E0). This cell line has the characteristic chromosome abnormality of M4E0, inv(16) (p13q22). When cultured in RPMI 1640 medium containing 10% fetal calf serum, ME-1 cells were monoblastoid, but with the addition of cytokines such as interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-4, or medium conditioned by phytohemagglutinin-stimulated human peripheral leukocytes (PHA-LCM), the cells exhibited differentiation to macrophage-like cells. PHA-LCM also promoted eosinophilic-lineage differentiation of this cell line, although IL-5 did not do so. To elucidate the mechanism of proliferation and differentiation of ME-1 cells, we studied the effect of a potent inhibitor of protein kinase C, 1-(5-isoquinolinyl-sulfonyl)-2- methylpiperazine (H-7), on colony formation of ME-1 cells. H-7 inhibited colony formation of ME-1 cells by IL-3 or GM-CSF dose dependently, but had little inhibitory effect on colony formation by IL- 4. These results indicate that the proliferation and differentiation of ME-1 cells by IL-3 or GM-CSF were related to the activation of protein kinase C, while those by IL-4 involved other regulatory systems. ME-1 cells should be useful for studying the pathogenesis of M4E0 and the mechanisms of proliferation and differentiation of leukemic and normal progenitors by cytokines.

HDAC1 Is a Required Cofactor of CBFβ-SMMHC and a Potential Therapeutic Target in Inversion 16 Acute Myeloid Leukemia

“…Because HDAC1 colocalizes with RUNX1 and CBFb-SMMHC on gene promoters, it is possible that HDAC1 is part of the RUNX1:CBFb-SMMHC complex. Before testing this, we confirmed that HDAC1 is expressed in leukemia cells from knockin mice with a conditional Cbfb-MYH11 allele (Cbfb þ/56M ) under the control of the Mx1-Cre Recombinase (Mx1-Cre þ ) transgene, (hereafter CM þ cells) and in the human inv(16) cell line, ME-1 (14,15,23,31). We detected increased levels of HDAC1 in three different CM þ mouse samples as compared with bone marrow from wild-type mice.…”

Identification of the chimeric protein product of the CBFB‐MYH11 fusion gene in inv(16) leukemia cells

“…Patient 2 was a 65-year-old man with a clinical diagnosis of AML-MlEo. Patient 3 had AML-M~Eo, whereas patient 4 had CML in blast crisis associated with eosinophilia (Yanagisawa et al, 1991;Evers et al, 1992). Patient 6 was a 34-year-old woman with a clinical diagnosis of AML-M4 without elevated eosinophil count.…”

“…Bone marrow samples were collected from all patients except patient 3. A cell line has been developed from patient 3 cells (Yanagisawa et al, 1991), and cultured cells were harvested for analysis.…”

CBFβ-MYH11 interferes with megakaryocyte differentiation via modulating a gene program that includes GATA2 and KLF1

“…To further explore the detailed functional pathways induced by CBFβ-MYH11 alone, we generated a stable dox-inducible CBFβ-MYH11 knockdown (KD) cell line based on the inv(16) cell line ME-1 25 (Figure 4A), and further examined genome-wide changes in the transcriptome as well as the acetylome. Previously, CBFβ-MYH11 transduction of CD34 + cells was shown to enhance proliferation 26 .…”