Endogenous bcl-2 is not required for the development of E mu-myc-induced B-cell lymphoma

Kelly, PN; Puthalakath, H; Adams, JM; Strasser, A

Author(s): Kelly, PN; Puthalakath, H; Adams, JM; Strasser, A;
Details: Publication Year 2007-06-01,Volume 109,Issue #11,Page 4907-4913
Journal Title: BLOOD
Publication Type: Journal Article
Abstract: Although myc and bcl-2 synergize in tumor development, particularly lymphomagenesis, it is not known whether endogenous bcl-2 is required for myc-induced tumorigenesis. To investigate the role of endogenous Bcl-2 in myc-induced lymphomagenesis, we bypassed the early death of Bcl-2-deficient mice by reconstituting lethally irradiated wild-type (wt) mice with a hematopoietic system from fetal liver-derived stem cells of E mu-mycl bcl-2(-/-) or control E mu-myc transgenic embryos. In premalignant (healthy) recipients, loss of Bcl-2 caused a moderate decrease in pre-B and immature B cells, and a dramatic reduction of mature B lymphocytes expressing the E mu-myc transgene. Furthermore, cultured preneoplastic E mu-myc/bcl-2(-1-) mature B cells displayed accelerated apoptosis compared with E mu-myc B cells. However, despite the striking reduction in B-cell numbers in vivo, ablation of endogenous Bcl-2 did not prevent or even delay development of E mu-myc lymphoma. Moribund mice presented with similar degrees of splenomegaly, blood leukocyte numbers, and tumor dissemination at death. These findings demonstrate that the initiation, development, continued growth, and severity of E mu-myc lymphoma do not depend upon endogenous Bcl-2, nor upon the total number of B lymphoid cells driven by the E mu-myc transgene. These results have implications for the treatment of hematopoietic tumors, particularly those that are not caused by Bcl-2 overexpression.
Publisher: AMER SOC HEMATOLOGY
Keywords: TRANSGENIC MICE; C-MYC; CHROMOSOME-TRANSLOCATION; REGULATED EXPRESSION; POLYCYSTIC KIDNEY; CYCLE PROGRESSION; PRE-B; DEATH; APOPTOSIS; LEUKEMIA
Publisher's Version: https://doi.org/10.1182/blood-2006-10051847
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2007-06-01 12:00:00