TY - JOUR
T1 - Tumor dormancy and cell signaling. V. Regrowth of the BCL1 tumor after dormancy is established
AU - Vitetta, Ellen S.
AU - Tucker, Thomas F.
AU - Racila, Emilian
AU - Huang, Yi Wu
AU - Marches, Radu
AU - Lane, Nancy
AU - Scheuermann, Richard H.
AU - Street, Nancy E.
AU - Watanabe, Takeshi
AU - Uhr, Jonathan W.
PY - 1997/6/15
Y1 - 1997/6/15
N2 - The majority of BALB/c mice immunized with the BCL1 lymphoma-derived idiotype (Id+) IgM and subsequently challenged with BCL1 tumor calls develop a state of tumor dormancy. The vest majority of dormant lymphoma cells are in cell cycle arrest, but there are also residual replicating cells. In the present studies, we attempted to define features of both the dormant lymphoma cells and the host that lead to escape from dormancy. Escape from dormancy occurs at a steady rate over a 2-year period, suggesting that it is s stochastic process. We found that, in the majority of mice, escape was due to the emergence of genetic variants that were no longer susceptible to the anti-Id-mediated induction of dormancy. Ten percent of these variants were Id-; the remainder were Id+ but could grow in the presence of anti-Id antibodies, suggesting that there were mutations in molecules involved in one or more mIg-mediated negative, signaling pathways. In two of five such escapees, alterations in either Syk, HS1, and/or Lyn were observed. In a small percentage of mice, a low titer of circulating anti-Id antibody before tumor challenge correlated with a subsequent, mere rapid loss of dormancy.
AB - The majority of BALB/c mice immunized with the BCL1 lymphoma-derived idiotype (Id+) IgM and subsequently challenged with BCL1 tumor calls develop a state of tumor dormancy. The vest majority of dormant lymphoma cells are in cell cycle arrest, but there are also residual replicating cells. In the present studies, we attempted to define features of both the dormant lymphoma cells and the host that lead to escape from dormancy. Escape from dormancy occurs at a steady rate over a 2-year period, suggesting that it is s stochastic process. We found that, in the majority of mice, escape was due to the emergence of genetic variants that were no longer susceptible to the anti-Id-mediated induction of dormancy. Ten percent of these variants were Id-; the remainder were Id+ but could grow in the presence of anti-Id antibodies, suggesting that there were mutations in molecules involved in one or more mIg-mediated negative, signaling pathways. In two of five such escapees, alterations in either Syk, HS1, and/or Lyn were observed. In a small percentage of mice, a low titer of circulating anti-Id antibody before tumor challenge correlated with a subsequent, mere rapid loss of dormancy.
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U2 - 10.1182/blood.v89.12.4425
DO - 10.1182/blood.v89.12.4425
M3 - Article
C2 - 9192767
AN - SCOPUS:0030912221
SN - 0006-4971
VL - 89
SP - 4425
EP - 4436
JO - Blood
JF - Blood
IS - 12
ER -