Elevated levels of cyclin A1 and A (A2) mRNA in acute myeloid leukaemia are associated with increased survival

Abstract

Summary. Cyclin A (A2) and cyclin A1 are members of the G 2 cyclins, which are involved in the control of G 2 /M and G 1 /S transitions as well as mitosis. Human cyclin A1 was cloned as an A-type cyclin that is highly expressed in acute myeloid leukaemia (AML). The clinical significance of these cyclins in myeloid leukaemia remains to be clarified. We investigated the relative levels of these transcripts in 80 patients with de novo AML. Correlations with clinical parameters showed that the initial white blood cell count and serum lactate dehydrogenase levels were inversely associated with cyclin A (A2) mRNA levels (r ¼ )0AE276, P ¼ 0AE019) and cyclin A1 mRNA levels (r ¼ )0AE241, P ¼ 0AE042) respectively. They were independently associated with increased overall survival [P ¼ 0AE035 for cyclin A (A2) and P ¼ 0AE016 for cyclin A1]. Multivariate analysis using Cox's proportional hazard model showed that elevated cyclin A1 mRNA levels contributed significantly to the better prognosis of patients with AML. Furthermore, the analysis of survival probability showed that the group with high levels of both cyclin A (A2) and A1 survived significantly longer than the group with low expression of both these cyclins (P ¼ 0AE002). These data indicate that high expression levels of both cyclin A (A2) and A1 are associated with good prognosis in AML patients.

Differential Peripheral Blood Gene Expression Profile Based on Her2 Expression on Primary Tumors of Breast Cancer Patients

“…A previous study showed that this gene is hypermethylated in white blood cells from cervical cancer patients, and has been associated with a more invasive phenotype [45]. In acute myeloid leukemia patients, high expression of Cyclin A1 mRNA was associated with increased survival [46].…”

Identification of genes with abnormal expression changes in acute myeloid leukemia

“…In these studies, high levels of WT1 and ILR3A expression were associated with unfavorable clinical outcomes, while increased expression of CCNA1 was associated with a favorable prognosis (Budel et al, 1989;Munoz et al, 2001;Testa et al, 2002;Nakamaki et al, 2003;Lapillonne et al, 2006). WT1 and CCNA1 have also been directly linked to leukemogenesis, with overexpression promoting leukemia in transgenic mice (Liao et al, 2001;Nishida et al, 2006).…”

“…Other studies have found an increased expression of CCNA1, IL3RA, and WT1 in AML patients (Budel et al, 1989;Schwarzinger et al, 1990;Marosi et al, 1992;Miwa et al, 1992;Miyagi et al, 1993;Inoue et al, 1994;Bergmann et al, 1997;Inoue et al, 1997;Schmid et al, 1997;Munoz et al, 2001;Testa et al, 2002;Nakamaki et al, 2003;Holm et al, 2006;Lapillonne et al, 2006;Steinbach et al, 2006). In these studies, high levels of WT1 and ILR3A expression were associated with unfavorable clinical outcomes, while increased expression of CCNA1 was associated with a favorable prognosis (Budel et al, 1989;Munoz et al, 2001;Testa et al, 2002;Nakamaki et al, 2003;Lapillonne et al, 2006).…”

“…Dysregulation of three of the 13 genes (CCNA1, TRIB2, WT1) has already been directly linked to leukemogenesis (Liao et al, 2001;Keeshan et al, 2006;Nishida et al, 2006), and three other genes (ALDH1A1, IL3RA, JAG1) are known to play critical roles in the regulation of normal hematopoiesis. In addition, expression changes in CCNA1, IL3RA, and WT1 may be associated with AML prognosis (Budel et al, 1989;Munoz et al, 2001;Testa et al, 2002;Nakamaki et al, 2003;Lapillonne et al, 2006). Most of the remaining 13 genes (BIK, FUT4, HOMER3, PLXNC1, SERPINB9, PELO, PRUNE), however, have not been studied in the context of hematopoiesis or leukemogenesis.…”

Cyclin A1 is a p53-induced gene that mediates apoptosis, G2/ M arrest, and mitotic catastrophe in renal, ovarian, and lung carcinoma cells

“…Abnormal expression of cyclin A1 has been associated with tumorigenesis. Human cyclin A1 is highly expressed in several types of acute myelogenous leukemia (AML) [12,13]. Abnormal myelopoiesis and AML developed in transgenic mice that overexpressed cyclin A1 [14].…”