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Transgenic Mice for MTCP1 Develop T-Cell Prolymphocytic
Leukemia
Catherine Gritti,
Hélène Dastot,
Jean Soulier,
Anne Janin,
Marie-Thérèse Daniel,
Ali Madani,
Gisèle Grimber,
Pascale Briand,
François Sigaux, and
Marc-Henri Stern
From INSERM U462 and Laboratoire Universitaire EA2378, Institut
Universitaire d'Hématologie, Hopital Saint Louis, Paris, France;
and INSERM U380, ICGM, Paris, France.
T-cell prolymphocytic leukemia (T-PLL) is a rare form of mature
T-cell leukemia associated with chromosomal rearrangements implicating
MTCP1 or TCL1 genes. These genes encode two homologous proteins, p13MTCP1 and p14TCL1,
which share no similarity with other known protein. To determine the
oncogenic role of MTCP1, mice transgenic for MTCP1
under the control of CD2 regulatory regions (CD2-p13 mice) were
generated. No abnormality was detected during the first year after
birth. A late effect of the transgene was searched for in a cohort of 48 CD2-p13 mice aged 15 to 20 months, issued from 3 independent founders. Lymphoid hemopathies, occurring in the three transgenic lines, were characterized by lymphoid cells with an irregular nucleus,
a unique and prominent nucleolus, condensed chromatin, a basophilic
cytoplasm devoid of granules, and an immunophenotype of mature T cells.
The molecular characterization of Tcrb rearrangements demonstrated the monoclonal origin of these populations.
Histopathological analysis of the cohort demonstrated early splenic and
hepatic infiltrations, whereas lymphocytosis and medullar infiltrations were found infrequently. The engraftment of these proliferations in
H2-matched animals demonstrated their malignant nature. Cumulative incidence of the disease at 20 months was 100%, 50%, and 21% in F3,
F4, and F7 lines, respectively, and null in the control group. The
level of expression of the transgene, as estimated by Western blotting
in the transgenic lines correlated with the tumoral incidence, with the
highest expression of p13MTCP1 being found in F3
mice. CD2-p13 transgenic mice developed an hemopathy similar to human
T-PLL. These data demonstrate that p13MTCP1 is an
oncoprotein and that CD2-p13 transgenic mice represent the first animal
model for mature T-PLL.
Blood, Vol. 92 No. 2 (July 15), 1998:
pp. 368-373
© 1998 by the American Society of Hematology.
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