Cyclin Al differs from other cyclins in its highly restricted expression pa
ttern. Besides its expression during spermatogenesis, cyclin Al is also exp
ressed in hematopoietic progenitor cells and in acute myeloid leukemia. We
investigated mechanisms that might contribute to cyclin Al expression in he
matopoietic cells, Comparison of cyclin Al and cyclin A promoter activity i
n adherent and myeloid leukemia cell lines showed that the cyclin Al promot
er is preferentially active in myeloid cell lines. This preferential activi
ty was present in a small, 335-bp cyclin Al promoter fragment that containe
d several potential c-myb binding sites. Coexpression of a c-myb expression
vector with the cyclin Al promoter constructs significantly increased the
reporter activity in adherent CV-1 as well as in myeloid U937 cells. Gel-sh
ift assays demonstrated that c-myb could bind to the cyclin Al promoter at
a binding site located near the transcription start site, Site-directed mut
agenesis of this site decreased promoter transactivation by 50% in both KCL
22 cells that express high levels of c-myb and in CV-1 cells that were tran
sfected with c-myb, In addition, transfection of primary human embryonic fi
broblasts with a c-myb expression vector led to induction of the endogenous
cyclin Al gene. Taken together, c-myb can directly transactivate the promo
ter of cyclin Al, and c-myb might be involved in the high-level expression
of cyclin Al observed in acute myeloid leukemia. These findings suggest tha
t c-myb induces hematopoiesis-specific mechanisms of cell cycle regulation.
(C) 1999 by The American Society of Hematology.