In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 98, No. 12 ( 2001-06-05), p. 6853-6858
Kurzfassung:
A mammalian A-type cyclin, cyclin A1, is highly expressed in testes of both human and mouse and targeted mutagenesis in the mouse has
revealed the unique requirement for cyclin A1 in the progression of male germ cells through the meiotic cell cycle. While very low levels
of cyclin A1 have been reported in the human hematopoietic system and brain, the sites of elevated levels of expression of human cyclin A1
were several leukemia cell lines and blood samples from patients with hematopoietic malignances, notably acute myeloid leukemia. To evaluate
whether cyclin A1 is directly involved with the development of myeloid leukemia, mouse cyclin A1 protein was overexpressed in the myeloid
lineage of transgenic mice under the direction of the human cathepsin G (hCG) promoter. The resulting transgenic mice exhibited an increased
proportion of immature myeloid cells in the peripheral blood, bone marrow, and spleen. The abnormal myelopoiesis developed within the
first few months after birth and progressed to overt acute myeloid leukemia at a low frequency (≈15%) over the course of 7–14 months.
Both the abnormalities in myelopoiesis and the leukemic state could be transplanted to irradiated SCID (severe combined immunodeficient) mice.
The observations suggest that cyclin A1 overexpression results in abnormal myelopoiesis and is necessary, but not sufficient in the
cooperative events inducing the transformed phenotype. The data further support an important role of cyclin A1 in hematopoiesis and the
etiology of myeloid leukemia.
Materialart:
Online-Ressource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.121540098
Sprache:
Englisch
Verlag:
Proceedings of the National Academy of Sciences
Publikationsdatum:
2001
ZDB Id:
209104-5
ZDB Id:
1461794-8
SSG:
11
SSG:
12
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