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Molecular requirements for rapid plasmacytoma and Pre‐B lymphoma induction by abelson murine leukemia virus in myc ‐transgenic mice
Author(s) -
Sugiyama Hiroyuki,
Wang Yisong,
Jackson Peter,
Sawyers Charles L.,
Klein George
Publication year - 1994
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910580122
Subject(s) - transgene , lymphoma , biology , microbiology and biotechnology , murine leukemia virus , fusion protein , mutant , abl , genetically modified mouse , cancer research , virus , virology , immunology , receptor , gene , biochemistry , recombinant dna , tyrosine kinase
Mutants and fusion products of the c‐abl gene were used to define some of the molecular requirements for rapid plasmacytoma (PC) and pre‐B‐lymphoma induction in pri5tane‐treated N‐ myc transgenic BALB/c mice. A‐MuLV induced PCs in 21 of 25 mice with a mean post‐pristane latency period of 46 ± 9 days, compared to 134 ± 25 days in controls exposed to pristane alone. ΔXB, a mutant of type IV c‐abi with a deletion of the SH3 domain, was equally effective in inducing PCs in 7 of 7 mice with a latency period of 49 ± 7 days, indicating that gag sequences are not required for rapid PC induction. The ΔXBΔNar mutant that carried a large C‐terminal deletion in addition showed only a negligible activity, if any, suggesting that PC acceleration requires the C‐terminal domain in the same way as lymphoid transformation and in contrast to fibroblast transformation. BCR‐ABL fusion constructs encoding an 185‐kDa protein as in acute leukemia, or a 210‐kDa protein as in chronic myelocytic leukemia (CML), did not accelerate pristane‐induced PC development in the N‐ mye transgenic mice, in contrast to their known ability to immortalize lymphoid cells in vitro. Only one of 14 non‐transgenic littermates developed a pre‐B lymphoma after A‐MuLV infection, and none of 10 normal littermates infected with ΔXB virus developed a construct‐carrying tumor. This result suggests that PC acceleration is due to co‐operative interaction of the N‐ myc transgene and activated abl. Infection of N‐myc transgenic bone marrow or spleen cells with A‐MuLV in vitro led to the outgrowth of pre‐B lymphonias after transplantation to pristine‐treated BALB/c recipients. The rymphoma‐inducing activity of A‐MuLV depends on its high titer, since diluted A‐MuLV or the lower‐titered ΔXB induced only PCs under the same conditions. The v‐abl , ΔXB and BCR‐ABL ‐carrying viruses generated immortalized lymphoblastoid lines in vitro , regardless of the presence of the N‐ myc transgene, suggesting that lymphoid transformation is a direct function of appropriate abl sequences in contrast to PC acceleration.