TY - JOUR
T1 - Development of a murine model for blastoid variant mantle-cell lymphoma
AU - Ford, Richard J.
AU - Shen, Long
AU - Lin-Lee, Yen Chiu
AU - Pham, Lan V.
AU - Multani, Asha
AU - Zhou, Hai Jun
AU - Tamayo, Archito T.
AU - Zhang, Chong Jie
AU - Hawthorn, Lesleyann
AU - Cowell, John K.
AU - Ambrus, Julian L.
N1 - Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2007/6/1
Y1 - 2007/6/1
N2 - Blastoid-variant mantle-cell lymphoma (MCL-BV), unlike most B-cell non-Hodgkin lymphomas (NHL-Bs), is refractory to conventional chemotherapy and associated with a very poor prognosis. Development of new therapies has been hampered by the lack of valid animal models. We have developed a novel murine model of MCL-BV by crossing interleukin 14α (IL-14α) transgenic mice with c-Myc transgenic mice (double transgenic [DTG]). IL-14α is a B-cell growth factor that is expressed in a number of high-grade lymphomas, including MCL-BV. Ninety-five percent of IL-14α transgenic mice develop CD5 + large B-cell lymphomas by 18 months of age. Sixty percent of c-Myc transgenic mice develop pre-B-cell lymphomas by 12 months of age. Close to 100% of DTG mice develop an aggressive, rapidly fatal lymphoma at 3 to 4 months of age that is CD5+, CD19+, CD21-, CD23 -, sIgM+. The tumor is found in the blood, bone marrow, liver, spleen, lymph nodes, gastrointestinal tract, and lungs and rarely in the brain, similar to the involvement seen in human MCL-BV. Immunoglobulin gene rearrangements document the monoclonality of the tumor. Cyclin D1 is highly expressed in these tumors, as it is in MCL-BV. DTG represents a novel model for MCL-BV that should reveal important insights into the pathogenesis of the lymphoma and contribute to the development of new forms of therapy.
AB - Blastoid-variant mantle-cell lymphoma (MCL-BV), unlike most B-cell non-Hodgkin lymphomas (NHL-Bs), is refractory to conventional chemotherapy and associated with a very poor prognosis. Development of new therapies has been hampered by the lack of valid animal models. We have developed a novel murine model of MCL-BV by crossing interleukin 14α (IL-14α) transgenic mice with c-Myc transgenic mice (double transgenic [DTG]). IL-14α is a B-cell growth factor that is expressed in a number of high-grade lymphomas, including MCL-BV. Ninety-five percent of IL-14α transgenic mice develop CD5 + large B-cell lymphomas by 18 months of age. Sixty percent of c-Myc transgenic mice develop pre-B-cell lymphomas by 12 months of age. Close to 100% of DTG mice develop an aggressive, rapidly fatal lymphoma at 3 to 4 months of age that is CD5+, CD19+, CD21-, CD23 -, sIgM+. The tumor is found in the blood, bone marrow, liver, spleen, lymph nodes, gastrointestinal tract, and lungs and rarely in the brain, similar to the involvement seen in human MCL-BV. Immunoglobulin gene rearrangements document the monoclonality of the tumor. Cyclin D1 is highly expressed in these tumors, as it is in MCL-BV. DTG represents a novel model for MCL-BV that should reveal important insights into the pathogenesis of the lymphoma and contribute to the development of new forms of therapy.
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U2 - 10.1182/blood-2006-08-038497
DO - 10.1182/blood-2006-08-038497
M3 - Article
C2 - 17311992
AN - SCOPUS:34249650739
VL - 109
SP - 4899
EP - 4906
JO - Blood
JF - Blood
SN - 0006-4971
IS - 11
ER -