Ayhan DEVİREN, Şeniz ÖNGÖREN, Seda EKİZOĞLU, R. Dilhan KURU, Ayşe ÇIRAKOĞLU, Şükriye YILMAZ, Yelda Tarkan ARGÜDEN

MDS/MPN olgusunda klonal evolüsyon gösteren kompleks karyotip bulguları

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. Gerçek zamanlı-polimeraz zincir tepkimesi 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 çekici olmuştur.

Complex karyotype with clonal evolution in a MDS/MPN case

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 appear to be a common finding in these diseases. In this study we present a MDS/ MPN case with complex karyotype. By Real Time-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 8 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 are considered important, being associated with carcinogenesis. BCL-2 family, whose members are important apoptosis regulators, is localized on the long arm of chromosome 18. Cytogenetic findings we present are remarkable as target regions in cancer genetics and alternative treatment research.

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