TEL-AML1, expressed from t(12;21) in human acute lymphocytic leukemia, induces acute leukemia in mice.
TEL-AML1 is expressed from the t(12;21) chromosomal translocation inB-precursor acute lymphocytic leukemia (ALL). Creation of the TEL-AML1fusion disrupts one copy of the TEL and AML1 genes, and loss of TEL or AML1 is also associated with cases of acute leukemia without TEL-AML1. To determine whether TEL-AML1 can contribute to leukemogenesis, we transduced marrow from C57BL/6 mice with a retroviral vector expressing TEL-AML1 or with a control vector. Transduced cells were introduced into irradiated syngeneic recipients. Two of 9 TEL-AML1 mice developed ALL (one T-lineage ALL and one B-precursor ALL), whereas 0 of 20 control mice developed leukemia. The B-precursor ALL was retransplantable and expressed TEL-AML1. We similarly transduced marrow from C57BL/6 mice lacking the overlapping p16(INK4a)p19(ARF) genes and transplanted the cells into wild-type recipients. No control mice died, but six of eight TEL-AML1/p16p19 mice died with leukemia. Overall, these findings indicate that TEL-AML1 contributes to leukemogenesis and may cooperate with loss of p16(INK4a)p14(ARF) to transform lymphoid progenitors.
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231, USA.
Florence
F
Bernardin
Yandan
Y
Yang
Rebecca
R
Cleaves
Marianna
M
Zahurak
Linzhao
L
Cheng
Curt I
CI
Civin
Alan D
AD
Friedman
D016475:3T3 Cells; D000818:Animals; D002881:Chromosomes, Human, Pair 12; D002891:Chromosomes, Human, Pair 21; D050676:Core Binding Factor Alpha 2 Subunit; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D017353:Gene Deletion; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007942:Leukemia, Experimental / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D012190:Retroviridae / Q000235:genetics; D014161:Transduction, Genetic; D014178:Translocation, Genetic; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics; D000097764:ETS Translocation Variant 6 Protein
D050676:Core Binding Factor Alpha 2 Subunit; D019941:Cyclin-Dependent Kinase Inhibitor p16; D015514:Oncogene Proteins, Fusion; D025803:Tumor Suppressor Protein p14ARF; C417743:Cdkn2a protein, mouse; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein