Improved coupling between proliferation‐arrest and differentiation‐induction in ML‐1 human myeloblastic leukemia cells

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Abstract
Proliferation and differentiation are coupled in normal cells and are aberrant in leukemia cells. The studies reported here were aimed at more effectively coupling proliferation‐arrest and differentiation‐incuction in a human myeloblastic leukemia cell line (ML‐1). This was accomplished by using reduced serum conditions in conjunction with a differentiation‐inducing agent: cells were first inncubated in reduced serum “0.3% fetal bovine serum (FBS)” instead of standard conditions (7.5% FBS) and, second, exposed to 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA). The effects of this protocol were as follows: first, cell proliferation was slowed and cells accumulated in Go/G1, phase of the cell cycle; this occurred with only a minimal decrease in viability “to∼88–92% (0.3% FBS) from ≥ 96% (7.5% FBS)”. Second, the induction of differentiation was accelerated; this allowed the time of exposure to TPA to be decreased. Acceleration of induction was very pronounced when cells were maintained in 0.3% FBS both before and during exposure to TPA, with TPA at concentrations above the minimum sufficient for induction but below those causing significant cytotoxicity; as little as 1 hour of TPA exposure resulted in near‐maximal induction (∼80%) with this protocol, compared to the ≥ 1 day required with previous standard protocols. In sum, conditions that slow ML‐1 cell proliferation (0.3% FBS) enhance TPA‐induced differentiation, substantially narrowing the time frame of induction; these conditions should be useful for studying the molecular mechanisms that underlie the induction process.