Effect of rapamycin on mouse chronic lymphocytic leukemia and the development of nonhematopoietic malignancies in Emu-TCL1 transgenic mice.
Chronic lymphocytic leukemia (CLL) is the most common leukemia in the world. The TCL1 gene, responsible for prolymphocytic T cell leukemia, is also overexpressed in human B cell malignancies and overexpression of the Tcl1 protein occurs frequently in CLL. Aging transgenic mice that overexpress TCL1 under control of the mu immunoglobulin gene enhancer, develop a CD5+ B cell lymphoproliferative disorder mimicking human CLL and implicating TCL1 in the pathogenesis of CLL. In the current study, we exploited this transgenic mouse to investigate two different CLL-related issues: potential treatment of CLL and characterization of neoplasms that accompany CLL. We successfully transplanted CLL cells into syngeneic mice that led to CLL development in the recipient mice. This approach allowed us to verify the involvement of the Tcl1/Akt/mTOR biochemical pathway in the disease by testing the ability of a specific pharmacologic agent, rapamycin, to slow CLL. We also showed that 36% of these transgenic mice were affected by solid malignancies, in which the expression of the Tcl1 protein was absent. These findings indicate that other oncogenic mechanism(s) may be involved in the development of solid tumors in Emu-TCL1 transgenic mice.
Zanesi
Nicola
N
Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, Ohio State University, 410 West 12th Avenue, Columbus, OH 43210, USA.
Aqeilan
Rami
R
Drusco
Alessandra
A
Kaou
Mohamed
M
Sevignani
Cinzia
C
Costinean
Stefan
S
Bortesi
Laura
L
La Rocca
Gaspare
G
Koldovsky
Pavel
P
Volinia
Stefano
S
Mancini
Rita
R
Calin
George
G
Scott
Charles P
CP
Pekarsky
Yuri
Y
Croce
Carlo M
CM
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D020123:Sirolimus / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D011518:Proto-Oncogene Proteins; C490393:Tcl1 protein, mouse; D020123:Sirolimus