MDS/MPN Tanılı Bir Olguda Klonal Evolüsyon Gösteren Kompleks Karyotip Bulguları

Yıl 2019, , 585 - 590, 30.09.2019

R. Dilhan Kuru , Ayşe Çırakoğlu , Şükriye Yılmaz Seda Ekizoğlu Yelda Tarkan Argüden Şeniz Öngören , Ayhan Deviren

https://doi.org/10.31362/patd.557577

Öz

Myelodisplastik /myeloproliferatif  neoplaziler (MDS/MPN) displastik ve
proliferatif özellikleri bir arada taşıyan klonal myeloid hastalıklardır.
MDS/MPN patofizyolojisi  myeloid
yolakların düzenlenmesindeki bozuklukları kapsamaktadır. En yaygın nedenlerin
başında 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 allele
özgü polimeraz zincir tepkimesi yöntemi ile 
JAK2  V617F 
mutasyonu  (+) saptanan  MDS/ MPN
ile uyumlu olgunun kemik iliği aspirasyon materyaline 24 ve 48 saatlik standart
hücre kültürü uygulanmıştır. GTL bantlama yöntemiyle yapılan sitogenetik
inceleme 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 de
içeren kompleks karyotip tespit edilmiştir. Yaptığımız literatür araştırmasında
hematolojik kanserlerde 18 ve 11 numaralı kromozomların katıldığı yeniden
düzenlenmeler gözlenirken, bu kromozom düzensizliklerinin kırık noktaları bizim
olgumuzdakinden farklı bulunmuştur. Trizomi/kısmi trizomi 18
lenfoproliferatif  hastalıklarda ve MDS
de gözlenen anomalilerden birisi olarak bildirilmektedir. Önemli apoptoz
düzenleyici gen ailelerinden biri olan Bcl-2,
18. kromozomun uzun kolunda yer almaktadır. Olgumuzda da  18. kromozomun uzun kolunun artışı söz
konusudur. Sunduğumuz sitogenetik bulgular kanser genetiği ve alternatif  tedavi araştırmalarında hedef bölge olması
açısından dikkat çekicidir.

Anahtar Kelimeler

MDS/MPN, kemik iliği, idic(18), trizomi 18, kromozom 11, kromozom 11 anomalileri

Complex Karyotype With Clonal Evolution In A MDS/MPN Case

Öz

Myelodysplastic/myeloproliferative
neoplasms (MDS/MPN) are clonal myeloid disorders that have both dysplastic and
proliferative features.  Pathophysiology
of MDS/MPN includes abnormalities in regulation of myeloid pathways. Patients
with MDS/MPN do not have BCR/ABL fusion gene. Abnormalities in
regulation of the ras pathway of signaling proteins appears to be a
common finding in these diseases.  In
this 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 complex
karyotype was observed with,
idic (18)(p11.2), t(11;idic(18))(p11.1;q11) and
dic(11;18)(q24;p11) which were formed through clonal evolution.  The results 
included  different rearrangements
and 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 disorders
and MDS. The genes on chromosome 18 considered 
important, as they are associated with carcinogenesis.  Bcl-2 family,
whose members are important apoptosis regulators, is localized on the long arm
of chromosome 18.

Anahtar Kelimeler

MDS/MPN, bone marrow, idic(18), trisomy 18, chromosome 11, chromosome 11 abnormalities

Kaynakça

• 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
• Referans2. Foucar K. Myelodysplastic/Myeloproliferative Neoplasms. Am J Clin Pathol 2009;132:281-289
• 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
• 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
• Referans5. ISCN (2016) An International System for Human Cytogenetic Nomenclature, McGowan-Jordan J., Simons A., Schmid M. (eds); S. Karger, Basel 2016
• 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.
• Referans7. Atlas of Genetics and Cytogenetics in Oncology and Haematology http://atlasgeneticsoncology.org/Anomalies/Anomliste.html
• 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
• 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
• 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
• 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
• 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
• 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
• 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