LEUKEMIC-CELL DIFFERENTIATION INVIVO AND INVITRO - ARREST OF PROLIFERATION PARALLELS THE DIFFERENTIATION INDUCED BY THE ANTILEUKEMIC DRUG HARRINGTONINE

  • 1 January 1984
    • journal article
    • research article
    • Vol. 63  (2) , 384-392
Abstract
A variety of chemical agents have been shown to induce differentiation in in vitro cultured neoplastic cell lines. Blast cells in the peripheral blood of acute nonlymphoid leukemia patients treated with the drug harringtonine appeared to undergo morphologic changes that suggested differentiation. In view of the relatively minimal myelotoxicity of harringtonine. Harringtonine was probably acting by differentiation-induction which concomitantly arrested cell division. This hypothesis was tested using 2 different experimental approaches. The [human] promyelocytic leukemic cell line, HL-60, was cultured with harringtonine and shown to differentiate into a cell, which by functional cell surface marker and morphologic criteria closely resembled normal monocytes. These changes were accompanied and slightly preceded by loss of proliferative capacity. Then, to prove that the leukemic blasts were the cells undergoing the changes observed in vivo, freshly isolated leukemia cell populations were cultured with harringtonine; morphologic changes paralleling those seen in the patients were observed. Thus, the antileukemic effect of harringtonine appeared to be due to diversion of the proliferating blast cells into a differentiation pathway, which, as in normal myeloid cells, resulted in the arrest of proliferation.

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