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Erschienen in: Wiener klinische Wochenschrift 1-2/2022

18.09.2020 | short report

CDC25c expression in patients with myelofibrosis is associated with stronger myeloproliferation and shorter overall survival

verfasst von: Davor Galusic, MD, Marko Lucijanic, MD, PhD, Ana Livun, PhD, Prof. Maja Radman, MD, PhD, Jelena Lucijanic, MD, Prof. Irena Drmic Hofman, PhD, Prof. Rajko Kusec, MD, PhD

Erschienen in: Wiener klinische Wochenschrift | Ausgabe 1-2/2022

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Summary

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.
Literatur
1.
Zurück zum Zitat Tefferi A, Lasho TL, Finke CM, et al. CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons. Leukemia. 2014;28(7):1472–7.CrossRef Tefferi A, Lasho TL, Finke CM, et al. CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons. Leukemia. 2014;28(7):1472–7.CrossRef
2.
Zurück zum Zitat Gheghiani L, Loew D, Lombard B, Mansfeld J, Gavet O. PLK1 Activation in Late G2 Sets Up Commitment to Mitosis. Cell Rep. 2017;19(10):2060–73.CrossRef Gheghiani L, Loew D, Lombard B, Mansfeld J, Gavet O. PLK1 Activation in Late G2 Sets Up Commitment to Mitosis. Cell Rep. 2017;19(10):2060–73.CrossRef
3.
Zurück zum Zitat Nikonova AS, Astsaturov I, Serebriiskii IG, Dunbrack RL Jr., Golemis EA. Aurora A kinase (AURKA) in normal and pathological cell division. Cell Mol Life Sci. 2013;70(4):661–87.CrossRef Nikonova AS, Astsaturov I, Serebriiskii IG, Dunbrack RL Jr., Golemis EA. Aurora A kinase (AURKA) in normal and pathological cell division. Cell Mol Life Sci. 2013;70(4):661–87.CrossRef
4.
Zurück zum Zitat Katayama H, Wang J, Treekitkarnmongkol W, et al. Aurora kinase—A inactivates DNA damage-induced apoptosis and spindle assembly checkpoint response functions of p73. Cancer Cell. 2012;21(2):196–211.CrossRef Katayama H, Wang J, Treekitkarnmongkol W, et al. Aurora kinase—A inactivates DNA damage-induced apoptosis and spindle assembly checkpoint response functions of p73. Cancer Cell. 2012;21(2):196–211.CrossRef
5.
Zurück zum Zitat Yang Q, Crispino JD, Wen QJ. Kinase signaling and targeted therapy for primary myelofibrosis. Exp Hematol. 2017;48:32–8.CrossRef Yang Q, Crispino JD, Wen QJ. Kinase signaling and targeted therapy for primary myelofibrosis. Exp Hematol. 2017;48:32–8.CrossRef
7.
Zurück zum Zitat Ozen M, Ittmann M. Increased expression and activity of CDC25C phosphatase and an alternatively spliced variant in prostate cancer. Clin Cancer Res. 2005;11(13):4701–6.CrossRef Ozen M, Ittmann M. Increased expression and activity of CDC25C phosphatase and an alternatively spliced variant in prostate cancer. Clin Cancer Res. 2005;11(13):4701–6.CrossRef
8.
Zurück zum Zitat Sur S, Agrawal DK. Phosphatases and kinases regulating CDC25 activity in the cell cycle: clinical implications of CDC25 overexpression and potential treatment strategies. Mol Cell Biochem. 2016;416(1–2):33–46.CrossRef Sur S, Agrawal DK. Phosphatases and kinases regulating CDC25 activity in the cell cycle: clinical implications of CDC25 overexpression and potential treatment strategies. Mol Cell Biochem. 2016;416(1–2):33–46.CrossRef
10.
Zurück zum Zitat Lucijanic M. Survival analysis in clinical practice: analyze your own data using an Excel workbook. Croat Med J. 2016;57(1):77–9.CrossRef Lucijanic M. Survival analysis in clinical practice: analyze your own data using an Excel workbook. Croat Med J. 2016;57(1):77–9.CrossRef
11.
Zurück zum Zitat Gautier EF, Picard M, Laurent C, et al. The cell cycle regulator CDC25A is a target for JAK2V617F oncogene. Blood. 2012;119(5):1190–9.CrossRef Gautier EF, Picard M, Laurent C, et al. The cell cycle regulator CDC25A is a target for JAK2V617F oncogene. Blood. 2012;119(5):1190–9.CrossRef
Metadaten
Titel
CDC25c expression in patients with myelofibrosis is associated with stronger myeloproliferation and shorter overall survival
verfasst von
Davor Galusic, MD
Marko Lucijanic, MD, PhD
Ana Livun, PhD
Prof. Maja Radman, MD, PhD
Jelena Lucijanic, MD
Prof. Irena Drmic Hofman, PhD
Prof. Rajko Kusec, MD, PhD
Publikationsdatum
18.09.2020
Verlag
Springer Vienna
Erschienen in
Wiener klinische Wochenschrift / Ausgabe 1-2/2022
Print ISSN: 0043-5325
Elektronische ISSN: 1613-7671
DOI
https://doi.org/10.1007/s00508-020-01738-2

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