1. ¹Division of Pathology, Department of Laboratory Medicine, Lund University, University Hospital, Malmö S-205 02 Sweden
2. ²Division of Molecular Medicine and Gene Therapy, BMC, Lund S-221 84 Sweden
3. ³Department of Genetics and Development, The Center for Reproductive Sciences and The Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York 10032, USA
4. ⁴Department of Obstetrics and Gynecology, The Center for Reproductive Sciences and The Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York 10032, USA

Correspondence: JL Persson, E-mail: jenny.persson@pat.mas.lu.se

Received 19 April 2004; Revised 9 August 2004; Accepted 13 August 2004; Published online 18 October 2004.

Abstract

An important role of the cell cycle regulatory protein cyclin A1 in the development of acute myeloid leukemia (AML) was previously demonstrated in a transgenic mouse model. We have now turned our attention to study specific aspects of the activity and subcellular distribution of cyclin A1 using bone marrow samples from normal donors and patients with AML, as well as leukemic cell lines. We show that the localization of cyclin A1 in normal hematopoietic cells is nuclear, whereas in leukemic cells from AML patients and cell lines, it is predominantly cytoplasmic. In leukemic cell lines treated with all-trans retinoic acid (ATRA), cyclin A1 localized to the nucleus. Further, there was a direct interaction between cyclin A1 and cyclin-dependent kinase 1, as well as a major ATRA receptor, RAR, in ATRA-treated cells but not in untreated leukemic cells. Our results indicate that the altered intracellular distribution of cyclin A1 in leukemic cells correlates with the status of the leukemic phenotype.