Inhibition of Proliferation and Induction of Differentiation of Human and Mouse Myeloid Leukemia Cells by New Ethyleneglycol‐type Nonphosphorus Alkyl Ether Lipids

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Abstract

A variety of ethyleneglycol‐type nonphosphorus alkyl ether lipids, ether derivatives of diethylene‐glycol in which the two hydroxyl groups were substituted with long chain alkyl and quaternary ammonioalkyl groups, were synthesized and their effects on proliferation and differentiation of cultured human (HL‐60) and mouse (M1) myeloid leukemia cells were studied. Incubation with these compounds inhibited the cellular proliferation, and the cells differentiated into morphologically and functionally mature granulocytes. Of the compounds tested, 1‐[2‐[2‐(octadecyloxy)ethoxy]ethoxy]‐butylpyridinium mesylate (EG‐6) was the most effective in inducing differentiation of HL‐60 cells. Almost maximal induction of differentiation and inhibition of growth of HL‐60 cells on day 6 were observed when the cells were treated with EG‐6 for 1 day and then cultured without EG‐6 for a further 5 days. The inhibitory effect of EG‐6 on the leukemic cells was over 100 times more than that of 2‐[2‐(dodecyloxy)ethoxy]ethyl 2‐pyridinioethyl phosphate, a potent antileukemic ether phospholipid.

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Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome.

C. Lozzio, B. Lozzio (1975)

A cell-line derived from a patient with chronic myelogenous leukemia (CML) is described. The new cell-line, which has over 175 serial passanges in a 3 1/2-yr period, has the following characteristics: (1) CML cells started to proliferate actively since they were first incubated in culture media. A threefold increase in the total number of cells was observed during the first seven passages; the cell population increased by a factor of 10 to 20 every 7 days from passage 8 through 85; from 20 to 40 times from passage 86 through 150, and more than 40 times after 150 passages. (2) The majority of the nononucleated cells are undifferentiated blasts. (3) The karyotype of all the cells examined show the Philadelphia (Ph1) chromosome and a long acrocentric marker plus aneuploidy. The Giemsa-banding studies identified the Ph1 chromosome as a terminal deletion of the long arm of chromosome 22:del(22)(q12) and the long acrocentric marker as an unbalanced reciprocal translocation of one chromosome 17 and the long arm of one chromosome 15. (4) The CML cells do not produce immunoglobulins, are free of mycoplasma, Epstein-Barr virus, and herpes-like virus particles. (5) CML cells have no alkaline phosphatase and myeloperoxidase activities and did not engulf inert particles. (6) Cultured CML cells provide a constant source of a specific antigen. This CML cell-line represents a unique source of CML cells with meaningful indicators of malignancy for clinical and experimental studies.