Myeloproliferation in long‐term plasmacytoma‐regressor mice

Abstract

MOPC-315 plasmacytoma-bearing BALB/c mice were treated with high doses of melphalan, causing a permanent and complete regression of the tumor. In the present study we analyzed plasmacytoma-regressor mice (PRM) 3-6 months after plasmacytoma regression. A second group of otherwise untreated normal mice was treated with melphalan (M--control group). A third group of mice remained untreated and served as an age- and sex-matched control group. PRM were cachectic and had an increased mortality rate compared to the M and the C control groups. Histopathological examination indicated that the spleen of PRM showed pronounced abnormalities, primarily in the red pulp. These abnormalities consisted of extramedullary hematopoiesis and myeloid-granulocytic hyperplasia. Spleens of M mice showed similar abnormalities but to a much lesser extent. Flow cytometric analysis of cellular surface markers of PRM splenocytes indicated a high number of large MAC-I- and GR-I-positive cells compared to splenocytes of M or C controls. These large cells also expressed Fc tau receptors (Fc tau RII), stained positively with non-specific esterase and adhered to plastic dishes; a certain percentage expressed MAC-2 and MAC-3 antigens. A quantitative suppression of CD4+ T cells and of B cells was also shown. Circulating levels of TNF were higher in PRM than in M or C mice. The capacity of splenocytes from PRM to secrete factors that stimulated CFU-GM colony formation in soft agar by bone-marrow cells from normal mice was significantly up-regulated compared to that of splenocytes from M or C mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Preleukemia in long‐term plasmacytoma‐regressor mice

“…Despite this wide range of immunohematopoietic abnormalities, no overt immunohematological malignancies were detected in PRM (Sagi et al, 1988;Sagi-Assif et al, 1994). However, we hereby report experimental results showing that PRM contain preleukemic cells.…”

“…PRM (i.e., mice in which the MOPC-315 plasmacytoma regressed following treatment with melphalan) (Sagi et al, 1988;Sagi-Assif et al, 1994) were originally developed as a potential animal model for therapy-related leukemia in melphalan-treated multiple myeloma patients. However, overt leukemia was never observed in these mice during an observation period of up to 12 months (Sagi et al, 1988).…”

“…In previous studies, we set out to segregate the contribution of chemotherapy from that of the primary tumor to the formation of secondary malignancies. We compared several immunohematopoietic parameters of melphalan chemotherapy-treated mice whose plasmacytoma tumor regressed following treatment with those of melphalan-treated normal mice (Sagi et al, 1988;Sagi-Assif et al, 1994). The former mice, designated hereafter as plasmacytoma-regressor mice (PRM), presented with abnormalities which were not evident or less so, in the chemotherapy-treated but otherwise normal mice.…”

“…Several abnormalities afflicting mainly or exclusively PRM which showed no signs of plasmacytoma relapse included (Sagi et al, 1988;Sagi-Assif et al, 1994) cachexia, early death, splenic myeloid-granulocytic hyperplasia and an increase in macrophagelike large splenocytes. These cells expressed specific macrophage markers and markers not usually expressed by unstimulated splenic macrophages.…”