Study of Cell Death in Friend Leukaemia

Abstract

Cell death of splenic Friend leukaemic cells has been studied in uivo, using 1251-UdR and 3H-TdR pulse labelling. The evolution of the splenic specific activity has been measured by autoradiography and external counting during 40 hr after injection of the labelled precursor. These two techniques show the existence of a large reutilization of. 3H-TdR (50 %), which is measurable as soon as 7 hr after the injection. The DNA turnover rate is rapid, 83.8% of the splenic cellular DNA being renewed per day. These results confirm that most of the cells produced in the Friend leukaemic spleen are rapidly lost; they also demonstrate that this cell loss is mainly due to a massive death, which occurs in proerythroblastic and erythroblastic compartments after one or two cell divisions.Friend leukaemic cells, which are characterized by a limited capacity of proliferation and a short lifespan, do not appear to be malignant.

Bcl-xL prevents apoptosis of late-stage erythroblasts but does not mediate the antiapoptotic effect of erythropoietin

“…31 In terms of splenic erythroblast turnover in mice with massive splenomegaly and ineffective erythropoiesis, splenic erythroblasts of mice with the acute erythroblastosis of Friend virus disease have been shown to have a daily turnover rate of 84%. 32 Wagner et al described nuclear and nonnuclear cellular debris in extracellular areas of spleens from conditional bcl-x Ϫ/Ϫ mice, 14 suggesting that some apoptotic erythroblasts may lyse prior to phagocytosis. Thus, in conditional bcl-x Ϫ/Ϫ mice, a steady state of 12% apoptotic TER-119 ϩ cells that are rapidly removed by phagocytosis or lysis coupled with high proliferative rates ( Figure 3) can result in complete turnover of a cohort of splenic erythroblasts in as little as 24 hours.…”

Erythroleukemic Differentiation

“…Initially consid ered to be a reticulum cell sarcoma (17,18) associated with a reactive erythroblastosis (19), it was suggested in 1962 by Zajdela (20), on the basis of both pathological studies and radio-iron uptake, that the primary disease initiated by Friend virus complex was a neoplastic proliferation of ery thropoietic elements. With both the Friend and the Mirand variants, the daily output of young red blood cells in infected animals is significantly augmented (24), and is associated with considerable ineffective erythropoie sis, a term for premature death of young nucleated erythroid cells (25,26). With both the Friend and the Mirand variants, the daily output of young red blood cells in infected animals is significantly augmented (24), and is associated with considerable ineffective erythropoie sis, a term for premature death of young nucleated erythroid cells (25,26).…”

Reflections on viruses and cancer

“…There are at least three instances where this is already known, the anaemias associated with Friend leukaemia in mice (Wollman et al, 1970;Smadja-Joffe et al, 1976), erythroblastosis in chickens (Darcel and Bather, 1964;Darcel and Bide, 1969;Darcel, 1973), and feline leukaemia (Mackey et al, 1975). The mechanisms by which the anaemias develop following infection with these leukaemia viruses have not, in my opinion, been completely elucidated.…”