Araştırma Makalesi
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Kronik Lenfositik Lösemide Aurora Kinaz A Ekspresyonu Değişikliği

Yıl 2020, Cilt: 7 Sayı: 1, 24 - 29, 28.04.2020

Öz

Aurora kinaz A, sentrozomların olgunlaşması ve ayrılmasını, mitoz sırasında iğ ipliklerinin oluşumu ve stabilitesini düzenleyen bir enzimdir. Aurora kinaz A’nın düzensizliği anöploidi ve kanser riskinde belirgin artış ile ilişkilidir. Bu çalışma, Aurora kinaz A ekspresyonunun kronik lenfositik lösemide (KLL) nasıl değiştiğini belirlemeyi amaçlamaktadır. Bu prospektif olgu-kontrol çalışmasında yeni tanı konmuş 41 KLL hastası ve benign hematolojik hastalıklara sahip 18 hasta değerlendirildi. Tüm hastalara kemik iliği aspirasyon ve biyopsisi uygulandı. Kemik iliği hücrelerinde Aurora kinaz A ekspresyonu, kantitatif ters transkriptaz-polimeraz zincir reaksiyonu ile belirlendi. Kemik iliği kesitleri immunhistokimyasal olarak Aurora-A antikoru için boyandı. KLL hastalarının kemik iliği aspiratlarında floresans insitu hibridizasyon yöntemiyle 13q delesyonu, 17p delesyonu ve trizomi 12 kromozom anomalileri araştırıldı. KLL hastaları ve benign hematolojik hastalığı olan hastalar, Aurora kinaz A mRNA ekspresyonu açısından istatistiksel olarak benzerdi (β-actin ve GAPDH housekeeping genleri için sırasıyla p=0.742 ve p=0.229). Aurora kinaz A için pozitif immunhistokimyasal boyanma KLL hastalarında anlamlı olarak daha sıktı (p<0.001). KLL hastalarının kemik iliği biyopsilerinde Aurora kinaz A immunhistokimyasal boyanması açısından, 13q delesyonu, 17p delesyonu veya trizomi 12 gibi sitogenetik anormaliklerle ilgili anlamlı farklılık gözlenmedi (p>0.05 her biri için). Aurora kinaz A, KLL patogenezinde rol oynayabilir ancak bu rol daha önce belirtildiği kadar belirgin olmayabilir.

Destekleyen Kurum

Adnan Menderes Üniversitesi Bilimsel Araştırma Projeleri Birimi

Proje Numarası

TPF-13009

Kaynakça

  • 1. Choi MY, Kashyap MK, Kumar D. The chronic lymphocytic leukemia microenvironment: Beyond the B-cell receptor. Best Pract Res Clin Haematol. 2016; 29(1):40–53.
  • 2. Galletti G, Caligaris-Cappio F, Bertilaccio MT. B cells and macrophages pursue a common path toward the development and progression of chronic lymphocytic leukemia. Leukemia. 2016; 30(12):2293–301.
  • 3. Alsagaby SA, Brennan P, Pepper C. Key molecular drivers of chronic lymphocytic leukemia. Clin Lymphoma Myeloma Leuk. 2016; 16(11):593–606.
  • 4. Wang G, Jiang Q, Zhang C. The role of mitotic kinases in coupling the centrosome cycle with the assembly of the mitotic spindle. J Cell Sci. 2014; 127(Pt 19):4111–22.
  • 5. Gavriilidis P, Giakoustidis A, Giakoustidis D. Aurora kinases and potential medical applications of Aurora kinase inhibitors: A review. J Clin Med Res. 2015; 7(10):742–51.
  • 6. Afonso O, Figueiredo AC, Maiato H. Late mitotic functions of Aurora kinases. Chromosoma. 2017; 126(1):93–103.
  • 7. Sen S, Katayama H, Sasai K. Functional significance of Aurora kinase A in centrosome amplification and genomic instability. Adv Exp Med Biol. 2008; 617:99–108.
  • 8. 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.
  • 9. Wang Y, Sun H, Wang Z, et al. Aurora-A: a potential DNA repair modulator. Tumour Biol. 2014; 35(4):2831–6.
  • 10. D'Assoro AB, Haddad T, Galanis E. Aurora-A Kinase as a promising therapeutic target in cancer. Front Oncol. 2016; 5:295.
  • 11. Treekitkarnmongkol W, Katayama H, Kai K, et al. Aurora kinase-A overexpression in mouse mammary epithelium induces mammary adenocarcinomas harboring genetic alterations shared with human breast cancer. Carcinogenesis. 2016; 37(12):1180–9.
  • 12. Zhang J, Li B, Yang Q, Zhang P, Wang H. Prognostic value of Aurora kinase A (AURKA) expression among solid tumor patients: a systematic review and meta-analysis. Jpn J Clin Oncol. 2015; 45(7):629–36.
  • 13. Casey NP, Fujiwara H, Ochi T, Yasukawa M. Novel immunotherapy for adult T-cell leukemia/lymphoma: Targeting aurora kinase A. Oncoimmunology. 2016; 5(11): e1239006.
  • 14. Wang LX, Wang JD, Chen JJ, et al. Aurora A kinase inhibitor AKI603 induces cellular senescence in chronic myeloid leukemia cells harboring T315I mutation. Sci Rep. 2016; 6: 35533.
  • 15. Kelly KR, Shea TC, Goy A, et al. Phase I study of MLN8237--investigational Aurora A kinase inhibitor--in relapsed/refractory multiple myeloma, non-Hodgkin lymphoma and chronic lymphocytic leukemia. Invest New Drugs. 2014; 32(3):489–99.
  • 16. Aradottir M, Reynisdottir ST, Stefansson OA, et al. Aurora A is a prognostic marker for breast cancer arising in BRCA2 mutation carriers. J Pathol Clin Res. 2014; 1(1):33–40.
  • 17. Oliveira FM, Lucena-Araújo AR, Leite-Cueva SD, Santos GA, Rego EM, Falcão RP. Segmental amplification of MLL gene associated with high expression of AURKA and AURKB genes in a case of acute monoblastic leukemia with complex karyotype. Cancer Genet Cytogenet. 2010; 198(1):62–5.
  • 18. Borges KS, Moreno DA, Martinelli CE Jr, et al. Spindle assembly checkpoint gene expression in childhood adrenocortical tumors (ACT): Overexpression of Aurora kinases A and B is associated with a poor prognosis. Pediatr Blood Cancer. 2013; 60(11):1809–16.
  • 19. Shinmura K, Kiyose S, Nagura K, et al. TNK2 gene amplification is a novel predictor of a poor prognosis in patients with gastric cancer. J Surg Oncol. 2014; 109(3):189–97.
  • 20. Koehrer S, Burger JA. B-cell receptor signaling in chronic lymphocytic leukemia and other B-cell malignancies. Clin Adv Hematol Oncol. 2016; 14(1):55–65.
  • 21. Seda V, Mraz M. B-cell receptor signalling and its crosstalk with other pathways in normal and malignant cells. Eur J Haematol. 2015; 94(3):193–205.
  • 22. Farag SS. The potential role of Aurora kinase inhibitors in haematological malignancies. Br J Haematol. 2011; 155(5):561–79.
  • 23. Durlacher CT, Li ZL, Chen XW, He ZX, Zhou SF. An update on the pharmacokinetics and pharmacodynamics of alisertib, a selective Aurora kinase A inhibitor. Clin Exp Pharmacol Physiol. 2016; 43(6):585–601.
  • 24. Inamdar KV, O'Brien S, Sen S, et al. Aurora-A kinase nuclear expression in chronic lymphocytic leukemia. Mod Pathol. 2008; 21(12):1428–35.
  • 25. de Paula Careta F, Gobessi S, Panepucci RA, et al. The Aurora A and B kinases are up-regulated in bone marrow-derived chronic lymphocytic leukemia cells and represent potential therapeutic targets. Haematologica. 2012; 97(8):1246–54.
  • 26. MacLean AL, Lo Celso C, Stumpf MP. Concise review: Stem cell population biology: Insights from hematopoiesis. Stem Cells. 2017; 35(1):80–8.
  • 27. Jan M, Ebert BL, Jaiswal S. Clonal hematopoiesis. Semin Hematol. 2017; 54(1):43–50.
  • 28. Herishanu Y, Pérez-Galán P, Liu D, et al. The lymph node microenvironment promotes B-cell receptor signaling, NF-kappa B activation, and tumor proliferation in chronic lymphocytic leukemia. Blood. 2011; 117(2):563–74.
  • 29. Ten Hacken E, Burger JA. Microenvironment interactions and B-cell receptor signaling in chronic lymphocytic leukemia: Implications for disease pathogenesis and treatment. Biochim Biophys Acta. 2016; 1863(3):401–13.
  • 30. Gry M, Rimini R, Strömberg S, et al. Correlations between RNA and protein expression profiles in 23 human cell lines. BMC Genomics. 2009; 10:365.
  • 31. Gygi SP, Rochon Y, Franza BR, Aebersold R. Correlation between protein and mRNA abundance in yeast. Mol Cell Biol. 1999; 19:1720–30.
  • 32. Tian Q, Stepaniants SB, Mao M, et al. Integrated genomic and proteomic analyses of gene expression in Mammalian cells. Mol Cell Proteomics. 2004; 3:960–9.
  • 33. Mehra A, Lee KH, Hatzimanikatis V. Insights into the relation between mRNA and protein expression patterns: I. Theoretical considerations. Biotechnol Bioeng. 2003; 84:822–33.
  • 34. Nie L, Wu G, Zhang W. Correlation of mRNA expression and protein abundance affected by multiple sequence features related to translational efficiency in Desulfovibrio vulgaris: a quantitative analysis. Genetics. 2006; 174:2229–43.
  • 35. Kelly KR, Shea TC, Goy A, et al. Phase I study of MLN8237--investigational Aurora A kinase inhibitor--in relapsed/refractory multiple myeloma, non-Hodgkin lymphoma and chronic lymphocytic leukemia. Invest New Drugs. 2014; 32(3):489–99.

How is Aurora Kinase A Expression Altered in Chronic Lymphocytic Leukemia?

Yıl 2020, Cilt: 7 Sayı: 1, 24 - 29, 28.04.2020

Öz

Aurora kinase A is an enzyme which regulates the maturation and separation of centrosomes and the assembly and stability of mitotic spindles during mitosis. The dysregulation of Aurora kinase A is related with aneuploidy and a pronounced increase in cancer risk. This study aims to determine how the expression of Aurora kinase A is altered in chronic lymphocytic leukemia (CLL). This prospective case-control study reviewed 41 patients who were newly diagnosed with CLL and 18 patients with benign hematological diseases. Bone marrow aspiration and biopsy were performed in all patients. Aurora kinase A expression in bone marrow cells was assessed by quantitative reverse transcriptase-polymerase chain reaction. Bone marrow specimens were immunohistochemically stained for Aurora-A antibody. Chromosomal abnormalities including 13q deletion, 17p deletion and trisomy 12 were investigated by fluorescence in situ hybridization in bone marrow aspirates of CLL patients. The CLL patients and the patients with benign hematological diseases were statistically similar in aspect of Aurora kinase A mRNA expression through β-actin and GAPDH housekeeping genes (respectively p=0.742 and p=0.229). Positive immunohistochemical staining for Aurora kinase A was significantly more frequent in CLL patients (p<0.001). Immunohistochemical staining for Aurora kinase A in bone marrow biopsies of CLL patients did not change significantly with respect to cytogenetic abnormalities such as 13q deletion, 17p deletion or trisomy 12 (p>0.05 for all). Aurora kinase A may play a role in the pathogenesis of CLL but this role may not be as evident as it has previously been specified.

Proje Numarası

TPF-13009

Kaynakça

  • 1. Choi MY, Kashyap MK, Kumar D. The chronic lymphocytic leukemia microenvironment: Beyond the B-cell receptor. Best Pract Res Clin Haematol. 2016; 29(1):40–53.
  • 2. Galletti G, Caligaris-Cappio F, Bertilaccio MT. B cells and macrophages pursue a common path toward the development and progression of chronic lymphocytic leukemia. Leukemia. 2016; 30(12):2293–301.
  • 3. Alsagaby SA, Brennan P, Pepper C. Key molecular drivers of chronic lymphocytic leukemia. Clin Lymphoma Myeloma Leuk. 2016; 16(11):593–606.
  • 4. Wang G, Jiang Q, Zhang C. The role of mitotic kinases in coupling the centrosome cycle with the assembly of the mitotic spindle. J Cell Sci. 2014; 127(Pt 19):4111–22.
  • 5. Gavriilidis P, Giakoustidis A, Giakoustidis D. Aurora kinases and potential medical applications of Aurora kinase inhibitors: A review. J Clin Med Res. 2015; 7(10):742–51.
  • 6. Afonso O, Figueiredo AC, Maiato H. Late mitotic functions of Aurora kinases. Chromosoma. 2017; 126(1):93–103.
  • 7. Sen S, Katayama H, Sasai K. Functional significance of Aurora kinase A in centrosome amplification and genomic instability. Adv Exp Med Biol. 2008; 617:99–108.
  • 8. 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.
  • 9. Wang Y, Sun H, Wang Z, et al. Aurora-A: a potential DNA repair modulator. Tumour Biol. 2014; 35(4):2831–6.
  • 10. D'Assoro AB, Haddad T, Galanis E. Aurora-A Kinase as a promising therapeutic target in cancer. Front Oncol. 2016; 5:295.
  • 11. Treekitkarnmongkol W, Katayama H, Kai K, et al. Aurora kinase-A overexpression in mouse mammary epithelium induces mammary adenocarcinomas harboring genetic alterations shared with human breast cancer. Carcinogenesis. 2016; 37(12):1180–9.
  • 12. Zhang J, Li B, Yang Q, Zhang P, Wang H. Prognostic value of Aurora kinase A (AURKA) expression among solid tumor patients: a systematic review and meta-analysis. Jpn J Clin Oncol. 2015; 45(7):629–36.
  • 13. Casey NP, Fujiwara H, Ochi T, Yasukawa M. Novel immunotherapy for adult T-cell leukemia/lymphoma: Targeting aurora kinase A. Oncoimmunology. 2016; 5(11): e1239006.
  • 14. Wang LX, Wang JD, Chen JJ, et al. Aurora A kinase inhibitor AKI603 induces cellular senescence in chronic myeloid leukemia cells harboring T315I mutation. Sci Rep. 2016; 6: 35533.
  • 15. Kelly KR, Shea TC, Goy A, et al. Phase I study of MLN8237--investigational Aurora A kinase inhibitor--in relapsed/refractory multiple myeloma, non-Hodgkin lymphoma and chronic lymphocytic leukemia. Invest New Drugs. 2014; 32(3):489–99.
  • 16. Aradottir M, Reynisdottir ST, Stefansson OA, et al. Aurora A is a prognostic marker for breast cancer arising in BRCA2 mutation carriers. J Pathol Clin Res. 2014; 1(1):33–40.
  • 17. Oliveira FM, Lucena-Araújo AR, Leite-Cueva SD, Santos GA, Rego EM, Falcão RP. Segmental amplification of MLL gene associated with high expression of AURKA and AURKB genes in a case of acute monoblastic leukemia with complex karyotype. Cancer Genet Cytogenet. 2010; 198(1):62–5.
  • 18. Borges KS, Moreno DA, Martinelli CE Jr, et al. Spindle assembly checkpoint gene expression in childhood adrenocortical tumors (ACT): Overexpression of Aurora kinases A and B is associated with a poor prognosis. Pediatr Blood Cancer. 2013; 60(11):1809–16.
  • 19. Shinmura K, Kiyose S, Nagura K, et al. TNK2 gene amplification is a novel predictor of a poor prognosis in patients with gastric cancer. J Surg Oncol. 2014; 109(3):189–97.
  • 20. Koehrer S, Burger JA. B-cell receptor signaling in chronic lymphocytic leukemia and other B-cell malignancies. Clin Adv Hematol Oncol. 2016; 14(1):55–65.
  • 21. Seda V, Mraz M. B-cell receptor signalling and its crosstalk with other pathways in normal and malignant cells. Eur J Haematol. 2015; 94(3):193–205.
  • 22. Farag SS. The potential role of Aurora kinase inhibitors in haematological malignancies. Br J Haematol. 2011; 155(5):561–79.
  • 23. Durlacher CT, Li ZL, Chen XW, He ZX, Zhou SF. An update on the pharmacokinetics and pharmacodynamics of alisertib, a selective Aurora kinase A inhibitor. Clin Exp Pharmacol Physiol. 2016; 43(6):585–601.
  • 24. Inamdar KV, O'Brien S, Sen S, et al. Aurora-A kinase nuclear expression in chronic lymphocytic leukemia. Mod Pathol. 2008; 21(12):1428–35.
  • 25. de Paula Careta F, Gobessi S, Panepucci RA, et al. The Aurora A and B kinases are up-regulated in bone marrow-derived chronic lymphocytic leukemia cells and represent potential therapeutic targets. Haematologica. 2012; 97(8):1246–54.
  • 26. MacLean AL, Lo Celso C, Stumpf MP. Concise review: Stem cell population biology: Insights from hematopoiesis. Stem Cells. 2017; 35(1):80–8.
  • 27. Jan M, Ebert BL, Jaiswal S. Clonal hematopoiesis. Semin Hematol. 2017; 54(1):43–50.
  • 28. Herishanu Y, Pérez-Galán P, Liu D, et al. The lymph node microenvironment promotes B-cell receptor signaling, NF-kappa B activation, and tumor proliferation in chronic lymphocytic leukemia. Blood. 2011; 117(2):563–74.
  • 29. Ten Hacken E, Burger JA. Microenvironment interactions and B-cell receptor signaling in chronic lymphocytic leukemia: Implications for disease pathogenesis and treatment. Biochim Biophys Acta. 2016; 1863(3):401–13.
  • 30. Gry M, Rimini R, Strömberg S, et al. Correlations between RNA and protein expression profiles in 23 human cell lines. BMC Genomics. 2009; 10:365.
  • 31. Gygi SP, Rochon Y, Franza BR, Aebersold R. Correlation between protein and mRNA abundance in yeast. Mol Cell Biol. 1999; 19:1720–30.
  • 32. Tian Q, Stepaniants SB, Mao M, et al. Integrated genomic and proteomic analyses of gene expression in Mammalian cells. Mol Cell Proteomics. 2004; 3:960–9.
  • 33. Mehra A, Lee KH, Hatzimanikatis V. Insights into the relation between mRNA and protein expression patterns: I. Theoretical considerations. Biotechnol Bioeng. 2003; 84:822–33.
  • 34. Nie L, Wu G, Zhang W. Correlation of mRNA expression and protein abundance affected by multiple sequence features related to translational efficiency in Desulfovibrio vulgaris: a quantitative analysis. Genetics. 2006; 174:2229–43.
  • 35. Kelly KR, Shea TC, Goy A, et al. Phase I study of MLN8237--investigational Aurora A kinase inhibitor--in relapsed/refractory multiple myeloma, non-Hodgkin lymphoma and chronic lymphocytic leukemia. Invest New Drugs. 2014; 32(3):489–99.
Toplam 35 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular İç Hastalıkları
Bölüm Araştırma Makalesi
Yazarlar

Deniz Çetin 0000-0001-9144-4018

Gökhan Pektaş 0000-0001-6590-6469

Gökay Bozkurt 0000-0002-6963-3186

Füruzan Kacar Bu kişi benim 0000-0002-6687-2966

İrfan Yavaşoğlu Bu kişi benim 0000-0003-1703-2175

Ali Bolaman Bu kişi benim 0000-0003-0651-5462

Gürhan Kadıköylü Bu kişi benim 0000-0001-9979-7475

Proje Numarası TPF-13009
Yayımlanma Tarihi 28 Nisan 2020
Gönderilme Tarihi 29 Ocak 2020
Yayımlandığı Sayı Yıl 2020 Cilt: 7 Sayı: 1

Kaynak Göster

APA Çetin, D., Pektaş, G., Bozkurt, G., Kacar, F., vd. (2020). How is Aurora Kinase A Expression Altered in Chronic Lymphocytic Leukemia?. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi, 7(1), 24-29.
AMA Çetin D, Pektaş G, Bozkurt G, Kacar F, Yavaşoğlu İ, Bolaman A, Kadıköylü G. How is Aurora Kinase A Expression Altered in Chronic Lymphocytic Leukemia?. MMJ. Nisan 2020;7(1):24-29.
Chicago Çetin, Deniz, Gökhan Pektaş, Gökay Bozkurt, Füruzan Kacar, İrfan Yavaşoğlu, Ali Bolaman, ve Gürhan Kadıköylü. “How Is Aurora Kinase A Expression Altered in Chronic Lymphocytic Leukemia?”. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi 7, sy. 1 (Nisan 2020): 24-29.
EndNote Çetin D, Pektaş G, Bozkurt G, Kacar F, Yavaşoğlu İ, Bolaman A, Kadıköylü G (01 Nisan 2020) How is Aurora Kinase A Expression Altered in Chronic Lymphocytic Leukemia?. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi 7 1 24–29.
IEEE D. Çetin, G. Pektaş, G. Bozkurt, F. Kacar, İ. Yavaşoğlu, A. Bolaman, ve G. Kadıköylü, “How is Aurora Kinase A Expression Altered in Chronic Lymphocytic Leukemia?”, MMJ, c. 7, sy. 1, ss. 24–29, 2020.
ISNAD Çetin, Deniz vd. “How Is Aurora Kinase A Expression Altered in Chronic Lymphocytic Leukemia?”. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi 7/1 (Nisan 2020), 24-29.
JAMA Çetin D, Pektaş G, Bozkurt G, Kacar F, Yavaşoğlu İ, Bolaman A, Kadıköylü G. How is Aurora Kinase A Expression Altered in Chronic Lymphocytic Leukemia?. MMJ. 2020;7:24–29.
MLA Çetin, Deniz vd. “How Is Aurora Kinase A Expression Altered in Chronic Lymphocytic Leukemia?”. Muğla Sıtkı Koçman Üniversitesi Tıp Dergisi, c. 7, sy. 1, 2020, ss. 24-29.
Vancouver Çetin D, Pektaş G, Bozkurt G, Kacar F, Yavaşoğlu İ, Bolaman A, Kadıköylü G. How is Aurora Kinase A Expression Altered in Chronic Lymphocytic Leukemia?. MMJ. 2020;7(1):24-9.