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 p16INK4A,
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.