Skip to main content
Article
Altered Myelopoiesis and the Development of Acute Myeloid Leukemia in Transgenic Mice Overexpressing Cyclin A1.
Proceedings of the National Academy of Sciences of the United States of America
  • Ching Liao
  • Xiang Yuan Wang
  • Hong Quan Wei
  • Taha Merghoub
  • Pier Paolo Pandolfi
  • Debra J Wolgemuth
  • Sherry Q Li, MD, Lehigh Valley Health Network
Publication/Presentation Date
6-5-2001
Abstract

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 ( approximately 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.

Disciplines
PubMedID
11381140
Document Type
Article
Citation Information

Liao, C., Wang, X. Y., Wei, H. Q., Li, S. Q., Merghoub, T., Pandolfi, P. P., & Wolgemuth, D. J. (2001). Altered myelopoiesis and the development of acute myeloid leukemia in transgenic mice overexpressing cyclin A1. Proceedings Of The National Academy Of Sciences Of The United States Of America, 98(12), 6853-6858.