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

Year 2019, Volume: 12 Issue: 3, 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

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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