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ATM-deficiency in the absence of T cells promotes the development of B cell lymphomas with dependence on NF-kB

Wednesday, November 06, 2013 — Poster Session I

4:00 p.m. – 6:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • K.S. Hathcock
  • H. Padilla-Nash
  • J. Camps
  • D. Triner
  • D-M. Shin
  • R.W. Maul
  • P.J. Gearhart
  • H.C. Morse
  • T. Ried
  • R.J. Hodes


The protein product of the ataxia-telangiectasia mutated gene, ATM, is a kinase that plays a central role in maintaining genomic integrity and protecting cells from oncogenic transformation. Mutations of the human ATM gene cause ataxia-telangiectasia, an autosomal recessive disorder that is associated with increased incidence of malignancies, especially lymphoid tumors. ATM-deficient mice have been useful tools to study thymic lymphomas, which occur at high frequency in these mice, but the early onset of these tumors has prevented analysis of other types of malignancies. In this study we generated ATM- and CD3ε-deficient mice that lacked T cells. These mice do not develop thymic lymphomas, but routinely develop B cell lymphomas that express surface markers characteristic of mature activated B cells. These B cell lymphomas resemble human diffuse large B cell (DLBC) lymphomas and possess complex karyotypes with genetic amplifications, deletions and unbalanced translocations. Interestingly all lymphomas (10/10) contain an amplification of a 5Mb region on chromosome 18 containing MALT1. These lymphomas express NF-kB and are dependent on MALT1 and NF-kb signaling for in vitro survival. As such they represent a mouse model for NF-kB- dependent human DLBC lymphomas of the ABC- subtype.

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