Non-malignant leukocytes delay spontaneous B-CLL cell apoptosis.

GAMBERALE R; GEFFNER J; ARROSAGARAY G; SCOLNIK M; SALAMONE G; TREVANI A; VERMEULEN M; GIORDANO M

LEUKEMIA

Año: 2001 vol. 15 p. 1860 - 1867

0887-6924

Malignant B cells from chronic lymphocytic leukemia (B-CLL)patients have a long survival in vivo, although, in culture, theyspontaneously die by apoptosis. Here, we analyzed thecapacity of accessory leukocytes to modulate apoptosis of BCLLcells in vitro. To this end, we performed long-term culturesusing total mononuclear cells (TMC) from B-CLL patients andTMC depleted from monocytes, NK cells and T lymphocytes (BCLLcells). In all the patients studied (n = 25) the presence ofaccessory leukocytes markedly prolonged the survival of BCLLcells. The anti-apoptotic effect was exerted by monocytesand, to a lesser degree, NK cells, partially through the releaseof soluble factors. Indeed, accessory leukocytes separatedfrom leukemic cells by semipermeable membranes were stillable to prolong B-CLL cell survival. By flow cytometric analysiswe found that the protective effect of non-malignant cells wasassociated with delayed down-regulation of Bcl-2 expressionon leukemic cells. By contrast, the expression of Fas and Fasligand proteins was unchanged in most samples. Our findingssuggest that monocytes and NK cells, by delaying leukemic cellapoptosis, may play a role in B-CLL cell accumulation in vivo.