BCR/ABL P210 and P190 cause distinct leukemia in transgenic mice.
DNA constructs encoding BCR/ABL P210 have been introduced into the mouse germ line using microinjection of one-cell fertilized eggs. Kinetics of BCR/ABL P210 expression in transgenic mice were very similar to those of BCR/ABL P190 constructs in transgenic mice. mRNA transcripts were detectable early in embryonic development and also in hematopoietic tissue of adult animals. Expression of BCR/ABL in peripheral blood preceded development of overt disease. P210 founder and progeny transgenic animals, when becoming ill, developed leukemia of B, T-lymphoid, or myeloid origin after a relatively long latency period. In contrast, P190-transgenic mice exclusively developed leukemia of B-cell origin, with a relatively short period of latency. The observed dissimilarities are most likely due to intrinsically different properties of the P190 and P210 oncoproteins and may also involve sequences that control transgene expression. The delayed progression of BCR/ABL P210-associated disease in the transgenic mice is consistent with the apparent indolence of human chronic myeloid leukemia during the chronic phase. We conclude that, in transgenic models, comparable expression of BCR/ABL P210 and BCR/ABL P190 results in clinically distinct conditions.
Department of Pathology Research and Laboratory Medicine, Childrens Hospital of Los Angeles, CA 90027, USA.
J W
JW
Voncken
V
V
Kaartinen
P K
PK
Pattengale
W T
WT
Germeraad
J
J
Groffen
N
N
Heisterkamp
D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology; D001483:Base Sequence; D001752:Blast Crisis / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D054278:Embryonal Carcinoma Stem Cells; D016044:Fusion Proteins, bcr-abl / Q000096:biosynthesis / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007942:Leukemia, Experimental / Q000235:genetics* / Q000473:pathology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000473:pathology; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D008970:Molecular Weight; D014411:Neoplastic Stem Cells / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D013601:T-Lymphocytes / Q000473:pathology; D019076:Transgenes
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011993:Recombinant Fusion Proteins; D008668:Metallothionein; D016044:Fusion Proteins, bcr-abl