Cloning and developmental expression of the murine homolog of the acute leukemia proto-oncogene AF4.
AF4 is the 4q21 gene involved in the acute lymphoblastic leukemia associated t(4;11)(q21;q23) where it forms a fusion gene with MLL. In order to gain insight into AF4's role in leukemogenesis we have studied its functional domains and expression pattern during murine development. We have cloned the murine homolog, Af4. We have demonstrated that 5' half of Af4 encodes a region with transcriptional transactivation activity which is disrupted by the t(4;11) in human leukemias. We have also localized the murine AF4 protein to the nucleus supporting a role for AF4 in transcription. The developmental expression pattern of Af4 was determined in situ hybridization and suggests Af4 plays an important role in the development of the hematopoietic, cardiovascular, skeletal and central nervous systems. A repeating pattern of Af4 expression in development is down-regulation with differentiation of a tissue. Among the cell types where this pattern of down-regulation is noted are B-lymphocytes. These findings raise the possibility that the disruption of normal AF4 function by the translocation may contribute to leukemogenesis.
Baskaran
K
K
Department of Pathology, University of Chicago, Illinois 60637, USA.
Erfurth
F
F
Taborn
G
G
Copeland
N G
NG
Gilbert
D J
DJ
Jenkins
N A
NA
Iannaccone
P M
PM
Domer
P H
PH
D000595:Amino Acid Sequence; D000818:Animals; D002880:Chromosomes, Human, Pair 11; D002894:Chromosomes, Human, Pair 4; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics; D000090063:Proto-Oncogene Mas; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions / Q000378:metabolism; D015533:Transcriptional Activation; D035602:Transcriptional Elongation Factors; D014178:Translocation, Genetic
C489900:Aff1 protein, mouse; D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D009687:Nuclear Proteins; D000090063:Proto-Oncogene Mas; D035602:Transcriptional Elongation Factors; C081449:AFF1 protein, human