Davor Galusic1, Marko Lucijanic2, Ana Livun3, Maja Radman4,5, Jelena Lucijanic6, Irena Drmic Hofman5,7, Rajko Kusec8,9,10. 1. Department of Hematology, University Hospital of Split, Soltanska 1, 21000, Split, Croatia. 2. Hematology Department, University Hospital Dubrava, Av. Gojka Suska 6, 10000, Zagreb, Croatia. 3. Clinical Institute of Laboratory Diagnosis, Division of Molecular Diagnosis and Genetics, University Hospital Dubrava, Av. Gojka Suska 6, 10000, Zagreb, Croatia. 4. Department of Endocrinology, University Hospital of Split, Soltanska 1, 21000, Split, Croatia. 5. School of Medicine, University of Split, Soltanska 2, 21000, Split, Croatia. 6. Health care center Zagreb-West, Prilaz baruna Filipovica 11, 10000, Zagreb, Croatia. 7. Department of Pathology, University Hospital of Split, Spinciceva 1, 21000, Split, Croatia. 8. Hematology Department, University Hospital Dubrava, Av. Gojka Suska 6, 10000, Zagreb, Croatia. rkusec@irb.hr. 9. Clinical Institute of Laboratory Diagnosis, Division of Molecular Diagnosis and Genetics, University Hospital Dubrava, Av. Gojka Suska 6, 10000, Zagreb, Croatia. rkusec@irb.hr. 10. School of Medicine, University of Zagreb, Salata 3, 10000, Zagreb, Croatia. rkusec@irb.hr.
Abstract
BACKGROUND: Cell division cycle 25c (CDC25c) is a gene coding a phosphatase controlling entry into mitosis upon activation through Polo-like kinase 1 (PLK1) and serves as a key regulator of cell division. The CDC25c was reported to be dysregulated in some malignant diseases, but its role in myelofibrosis has not yet been elucidated. METHODS: We have retrospectively investigated CDC25c mRNA expression in bone marrow aspirates of 43 patients with myelofibrosis (28 primary [PMF] and 15 secondary myelofibrosis [SMF]) and 12 controls. RESULTS: CDC25c mRNA expression did not significantly differ between PMF, SMF and controls (median ∆CT 3.08 vs 2.86 vs 2.29 for PMF, SMF and controls, respectively; P = 0.162). Patients presenting with higher CDC25c mRNA expression were of older age (P = 0.037), had statistically significantly higher white-blood-cells (P = 0.017), larger liver size (P = 0.022), higher absolute neutrophil (P = 0.010), monocyte (P = 0.050), basophil (P = 0.012), and eosinophil counts (P = 0.013). Patients presenting with high CDC25c mRNA expression had statistically significantly inferior overall survival compared to low CDC25c expression group (HR = 2.99; P = 0.049). Median overall survival was not reached in patients with low and was 44 months in patients with high CDC25c expression. CONCLUSION: Our data suggest that higher CDC25c expression is associated with more proliferative phenotype of myelofibrosis and is prognostic of worse survival. Future studies investigating these interesting associations are warranted.
BACKGROUND: Cell division cycle 25c (CDC25c) is a gene coding a phosphatase controlling entry into mitosis upon activation through Polo-like kinase 1 (PLK1) and serves as a key regulator of cell division. The CDC25c was reported to be dysregulated in some malignant diseases, but its role in myelofibrosis has not yet been elucidated. METHODS: We have retrospectively investigated CDC25c mRNA expression in bone marrow aspirates of 43 patients with myelofibrosis (28 primary [PMF] and 15 secondary myelofibrosis [SMF]) and 12 controls. RESULTS: CDC25c mRNA expression did not significantly differ between PMF, SMF and controls (median ∆CT 3.08 vs 2.86 vs 2.29 for PMF, SMF and controls, respectively; P = 0.162). Patients presenting with higher CDC25c mRNA expression were of older age (P = 0.037), had statistically significantly higher white-blood-cells (P = 0.017), larger liver size (P = 0.022), higher absolute neutrophil (P = 0.010), monocyte (P = 0.050), basophil (P = 0.012), and eosinophil counts (P = 0.013). Patients presenting with high CDC25c mRNA expression had statistically significantly inferior overall survival compared to low CDC25c expression group (HR = 2.99; P = 0.049). Median overall survival was not reached in patients with low and was 44 months in patients with high CDC25c expression. CONCLUSION: Our data suggest that higher CDC25c expression is associated with more proliferative phenotype of myelofibrosis and is prognostic of worse survival. Future studies investigating these interesting associations are warranted.
Authors: Davor Galusic; Marko Lucijanic; Ana Livun; Maja Radman; Viktor Blaslov; Lucana Vicelic Cutura; Marija Petric; Antonija Miljak; Jelena Lucijanic; Irena Drmic Hofman; Rajko Kusec Journal: Blood Cells Mol Dis Date: 2019-12-05 Impact factor: 3.039