Cyclin A1 is predominantly expressed in hematological malignancies with myeloid differentiation

Abstract

Cyclin A is a cell cycle regulatory protein that functions in mitotic and S phase control in mammalian cells. However, in contrast to other G₁ phase regulatory proteins, such as cyclin D, retinoblastoma protein and p16^INK4A, cyclin A seems not to be commonly involved in tumorigenesis. Recently, a second human cyclin A – cyclin A1 – has been identified. In contrast to cyclin A which is expressed throughout embryonic development and in adult tissue, the expression of cyclin A1 has been reported to be restricted to embryonic and germ line cells. We have confirmed the absence of cyclin A1 mRNA from normal peripheral blood leukocytes of seven healthy donors by single step reverse transcriptase-polymerase chain reaction (RT-PCR). Furthermore, we have examined the expression of cyclin A1 mRNA in 173 peripheral blood samples of 162 patients with various hematological malignancies. Cyclin A1 mRNA was detectable in 11 of 11 patients with acute myeloid leukemia, three of three patients with acute biphenotypic leukemia, eight of eight patients with myelodysplastic syndrome, 59 of 69 patients with chronic myelogenous leukemia (CML) at diagnosis, 13 of 15 patients with CML in blastic transformation, 10 of 18 patients with chronic lymphocytic leukemia, two of nine patients with essential thrombocythemia, and only two of 10 patients with acute lymphoblastic leukemia (ALL) with both cyclin A1 RT-PCR positive ALL leukemias being undifferentiated relapses. In addition, cyclin A1 mRNA was found in one of six leukapheresis products, harvested from individuals without hematological disorders. Taken together, cyclin A1 is expressed in the majority of myeloid and undifferentiated hematological malignancies as well as in normal hematopoietic progenitor cells. We conclude that cyclin A1, a protein potentially involved in G₁/S phase progression of immature cells, might be necessary for proliferation of early hematopoietic progenitor cells and their leukemic counterparts being blocked at that stage of differentiation.