Development of a murine model for blastoid variant mantle-cell lymphoma.
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 14alpha (IL-14alpha) transgenic mice with c-Myc transgenic mice (double transgenic [DTG]). IL-14alpha is a B-cell growth factor that is expressed in a number of high-grade lymphomas, including MCL-BV. Ninety-five percent of IL-14alpha 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.
Ford
Richard J
RJ
Department of Hematopathology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Shen
Long
L
Lin-Lee
Yen Chiu
YC
Pham
Lan V
LV
Multani
Asha
A
Zhou
Hai-Jun
HJ
Tamayo
Archito T
AT
Zhang
ChongJie
C
Hawthorn
Lesleyann
L
Cowell
John K
JK
Ambrus
Julian L
JL
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D007136:Immunoglobulins / Q000235:genetics; D007621:Karyotyping; D020522:Lymphoma, Mantle-Cell / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism
D007136:Immunoglobulins; D016328:NF-kappa B; D016271:Proto-Oncogene Proteins c-myc; D018123:Receptors, Interleukin; C094343:interleukin-14 receptor