TY - JOUR T1 - MDS/MPN Tanılı Bir Olguda Klonal Evolüsyon Gösteren Kompleks Karyotip Bulguları TT - Complex Karyotype With Clonal Evolution In A MDS/MPN Case AU - Kuru, R. Dilhan AU - Çırakoğlu, Ayşe AU - Yılmaz, Şükriye AU - Ekizoğlu, Seda AU - Tarkan Argüden, Yelda AU - Öngören, Şeniz AU - Deviren, Ayhan PY - 2019 DA - September Y2 - 2019 DO - 10.31362/patd.557577 JF - Pamukkale Medical Journal JO - Pam Med J PB - Pamukkale Üniversitesi WT - DergiPark SN - 1308-0865 SP - 585 EP - 590 VL - 12 IS - 3 LA - tr AB - Myelodisplastik /myeloproliferatif neoplaziler (MDS/MPN) displastik veproliferatif özellikleri bir arada taşıyan klonal myeloid hastalıklardır.MDS/MPN patofizyolojisi myeloidyolakların düzenlenmesindeki bozuklukları kapsamaktadır. En yaygın nedenlerinbaşında ras yolağı sinyal proteinlerindeki düzensizlikler gelir. Bu hastalarda BCR/ABL füzyon geni negatiftir. Real Time-Polimeraz Zincir Tepkimesi (RT-PCR) ile BCR/ABL p210 transkripti (-) ve alleleözgü polimeraz zincir tepkimesi yöntemi ileJAK2 V617Fmutasyonu (+) saptanan MDS/ MPNile uyumlu olgunun kemik iliği aspirasyon materyaline 24 ve 48 saatlik standarthücre kültürü uygulanmıştır. GTL bantlama yöntemiyle yapılan sitogenetikinceleme sonucunda, klonal evolüsyon ile meydana gelen idic(18)(p11.2),t(11;idic)(18))(p11.1;q11) ve dic(11;18)(q24;p11) yeniden düzenlenmelerini deiçeren kompleks karyotip tespit edilmiştir. Yaptığımız literatür araştırmasındahematolojik kanserlerde 18 ve 11 numaralı kromozomların katıldığı yenidendüzenlenmeler gözlenirken, bu kromozom düzensizliklerinin kırık noktaları bizimolgumuzdakinden farklı bulunmuştur. Trizomi/kısmi trizomi 18lenfoproliferatif hastalıklarda ve MDSde gözlenen anomalilerden birisi olarak bildirilmektedir. Önemli apoptozdüzenleyici gen ailelerinden biri olan Bcl-2,18. kromozomun uzun kolunda yer almaktadır. Olgumuzda da 18. kromozomun uzun kolunun artışı sözkonusudur. Sunduğumuz sitogenetik bulgular kanser genetiği ve alternatif tedavi araştırmalarında hedef bölge olmasıaçısından dikkat çekicidir. KW - MDS/MPN KW - kemik iliği KW - idic(18) KW - trizomi 18 KW - kromozom 11 KW - kromozom 11 anomalileri N2 - Myelodysplastic/myeloproliferativeneoplasms (MDS/MPN) are clonal myeloid disorders that have both dysplastic andproliferative features. Pathophysiologyof MDS/MPN includes abnormalities in regulation of myeloid pathways. Patientswith MDS/MPN do not have BCR/ABL fusion gene. Abnormalities inregulation of the ras pathway of signaling proteins appears to be acommon finding in these diseases. Inthis study we present a MDS/MPN case with complex cytogenetics. By Real Time-PCR (RT-PCR), BCR/ABL p210 transcript(MBCR) was negative, and by allele-specfic PCR, JAK2 V617F mutation was positive. By cytogenetics, a complexkaryotype was observed with,idic (18)(p11.2), t(11;idic(18))(p11.1;q11) anddic(11;18)(q24;p11) which were formed through clonal evolution. The resultsincluded different rearrangementsand partial gain of chromosome 18. Rearrangements involving chromosomes 11 and 18 have been previously reported in hematological malignancies but with different breakpoints from ours.Trisomy/ partial trisomy 18 had been reported in lymphoproliferative disordersand MDS. The genes on chromosome 18 consideredimportant, as they are associated with carcinogenesis. Bcl-2 family,whose members are important apoptosis regulators, is localized on the long armof chromosome 18. CR - Referans1. Vardiman JW, Harris N L and Brunning R D. TheWorld Health Organization (WHO) classification of the myeloid neoplasms. Blood 2002, 100 (7): 2292-302 CR - Referans2. Foucar K. Myelodysplastic/Myeloproliferative Neoplasms. Am J Clin Pathol 2009;132:281-289 CR - Referans3. Go´mez-Seguı´ I, H Makishima, A Jerez, K Yoshida. Novel recurrent mutations in the RAS-like GTP-binding gene RIT1 in myeloid malignancies. Leukemia (2013), 27(3); 1943 – 1946 CR - Referans4. Bacher U, Schnittger S, Kern W, Weiss T. Distribution of cytogenetic abnormalities in myelodysplastic syndromes, Philadelphia negative myeloproliferative neoplasms, and the overlap MDS/MPN category. Ann Hematol (2009) 88:1207–1213 CR - Referans5. ISCN (2016) An International System for Human Cytogenetic Nomenclature, McGowan-Jordan J., Simons A., Schmid M. (eds); S. Karger, Basel 2016 CR - Referans6. DiNardo CD, Daver N, Jain N et al. Myelodysplastic/Myeloproliferative Neoplasms, Unclassifiable (MDS/MPN, U): Natural history and clinical outcome by treatment strategy Leukemia. 2014 April ; 28(4): 958–961. CR - Referans7. Atlas of Genetics and Cytogenetics in Oncology and Haematology http://atlasgeneticsoncology.org/Anomalies/Anomliste.html CR - Referans8. Kominato S, Nakayama T, Sato F, Yamada S, Xia H. Characterization of chromosomal aberrations in thymic MALT lymphoma. Pathology International 2012; 62: 93–98 CR - Referans9. Dunlap J, Kelemen K, Leeborg N, Braziel R, Olson S, Press R. Association of JAK2 Mutation Status and Cytogenetic Abnormalities in Myeloproliferative Neoplasms and Myelodysplastic/Myeloproliferative Neoplasms. Am J Clin Pathol 2011;135:709-719 CR - Referans10. Slovak M L, Smith D D, Bedell V , Hsu Y-H, O’Donnell M. Assessing karyotype precision by microarray based comparative genomic hybridization in the myelodysplastic/myeloproliferative syndromes. Molecular Cytogenetics 2010, 3:23 CR - Referans11. Zhu D, Ikpatt OF, Dubovy SR et al. Molecular and genomic aberrations in Chlamydophila psittaci negative ocular adnexal marginal zone lymphomas. American Journal of Hematology 2013 sep;88(9):730-5 CR - Referans12. Deviren A, Gürsel İM ,Kuru D et al. Cytogenetic Evaluation in 221 Untreated Patients with Myelodysplastic Syndrome Tedavi Almamış 221 Miyelodisplastik Sendromlu Hastada Sitogenetik Değerlendirme Turkiye Klinikleri J Med Sci 2012;32(1):15-23 CR - Referans13. Parker JE, Mufti GJ, Rasool F, Mijovic A, Devereux S and Pagliuca A. The role of apoptosis, proliferation, and the Bcl-2–related proteins in the myelodysplastic syndromes and acute myeloid leukemia secondary to MDS. Blood 2000 ,vol. 96(12),3932-38 CR - Referans14. Bogenberger JM, Kornblau SM, Pierceall WE et al. BCL-2 family proteins as 5-Azacytidine-sensitizing targets and determinants of response in myeloid malignancies Leukemia (2014) 28, 1657–1665 UR - https://doi.org/10.31362/patd.557577 L1 - https://dergipark.org.tr/tr/download/article-file/823699 ER -