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

Abstract

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.

Keywords

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

Complex Karyotype With Clonal Evolution In A MDS/MPN Case

Abstract

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.

Keywords

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

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