A novel retrovirus provides the cooperating oncogenic event(s) required to demonstrate the tumor suppressor activity of p15Ink4b in myeloid cells in vivo.
Cancer is a multistep process resulting from an accumulation of several genetic changes. The determination of cooperating events in experimental models can help scientists decipher specific neoplastic pathways and place genes with similar functions in complementation groups. In leukemia models, retrovirus tagging is a powerful approach to determine genes that cooperate with oncogenic transgenes or tumor suppressors that have undergone targeted deletion. Experimental models for B and T cell leukemias involving transgenic c-myc were the first to show the utility of retroviral tagging. Here we review these experiments and present examples of new models of myeloid leukemia where retroviruses have collaborated with a transgene [Cbfbeta-MYH111 from Inv(16)] and with loss of a tumor suppressor (Ink4b) mice to induce disease.
Wolff
Linda
L
Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892-4255, USA. lwolff@helix.nih.gov
Garin
Matthew T
MT
Koller
Richard
R
Bies
Juraj
J
Tessarollo
Lino
L
Anver
Miriam R
MR
Powell
Douglas
D
Perella
Christine
C
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D050762:Cyclin-Dependent Kinase Inhibitor p15; D007938:Leukemia / Q000209:etiology* / Q000235:genetics / Q000821:virology; D015448:Leukemia, B-Cell / Q000209:etiology / Q000235:genetics / Q000821:virology; D007951:Leukemia, Myeloid / Q000209:etiology / Q000235:genetics / Q000821:virology; D015458:Leukemia, T-Cell / Q000209:etiology / Q000235:genetics / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000378:metabolism; D012190:Retroviridae / Q000502:physiology*; D019076:Transgenes; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*
C493968:Cdkn2b protein, mouse; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D025521:Tumor Suppressor Proteins