ISSN: 1300-7777 E-ISSN: 1308-5263
Variant Philadelphia translocations with different breakpoints in six chronic myeloid leukemia patients [Turk J Hematol]
Turk J Hematol. 2011; 28(3): 186-192 | DOI: 10.5152/tjh.2011.52  

Variant Philadelphia translocations with different breakpoints in six chronic myeloid leukemia patients

Dilhan Kuru1, Yelda Tarkan Argüden1, Muhlis Cem Ar3, Ayşe Çırakoğlu1, Şeniz Öngören3, Şükriye Yılmaz1, Ahmet Emre Eşkazan3, Ayhan Deviren2, Teoman Soysal3, Seniha Hacıhanefioğlu2, Birsen Ülkü3
1Department Of Medical Biology, Cerrahpaşa Faculty Of Medicine, İstanbul University, İstanbul, Turkey
2Department Of Medical Genetics, Cerrahpaşa Faculty Of Medicine, İstanbul University, İstanbul, Turkey
3Department Of Internal Medicine, Division Of Hematology, Cerrahpaşa Faculty Of Medicine, İstanbul University, İstanbul, Turkey

OBJECTIVE: The Philadelphia (Ph) chromosome, consisting of the t(9;22)(q34;q11) translocation, is observed in ~90% of patients with chronic myeloid leukemia (CML). Variant Ph translocations are observed in 5%-10% of CML patients. In variant translocations 3 and possibly more chromosomes are involved. Herein we report 6 CML patients with variant Ph translocations.
METHODS: Bone marrow samples were examined using conventional cytogenetic meth ods. Fluorescence in situ hybridization (FISH) with whole-chromosome paints and BCR-ABL 1D probes were used to confirm and/or complement the findings, and identify rearrangements beyond the resolution of conventional cytogenetic methods.
RESULTS: Variant Ph translocations in the 6 patients were as follows: t(7;22)(p22;q11), t(9;22;15)(q34;q11;q22), t(15;22)(p11;q11), t(1;9;22;3)(q24;q34;q11;q21), t(12;22)(p13;q11), and t(4;8;9;22)(q11;q13;q34;q11).
CONCLUSION: Among the patients, 3 had simple and 3 had complex variant Ph translocations. Two of the presented cases had variant Ph chromosomes not previously described, 1 of which had a new complex Ph translocation involving chromosomes 1, 3, 9, 22, and t(1;9;22;3)(q24;q34;q11;q21) apart from a clone with a classical Ph, and the other case had variant Ph translocation with chromosomes 4, 8, 9, and 22, and t(4;8;9;22)(q11;q13;q34;q11) full complex translocation. Number of studies reported that some patients with variant Ph translocation were poor responders to imatinib. All of our patients with variant Ph translocations had suboptimal responses to imatinib, denoting a poor prognosis also. Variant Ph translocations may be important as they are associated with prognosis and therapy for CML patients.

Keywords: Chronic myeloid leukemia (CML), variant Ph chromosome, cytogenetics, fluorescence in situ hybridization (FISH)


Altı Kronik miyeloid lösemi olgusunda farklı kırık noktalı varyant Philadelphia translokasyonları

Dilhan Kuru1, Yelda Tarkan Argüden1, Muhlis Cem Ar3, Ayşe Çırakoğlu1, Şeniz Öngören3, Şükriye Yılmaz1, Ahmet Emre Eşkazan3, Ayhan Deviren2, Teoman Soysal3, Seniha Hacıhanefioğlu2, Birsen Ülkü3
1İstanbul Üniversitesi Cerrahpaşa Tıp Fakultesi, Tıbbi Biyoloji Ana Bilim Dalı, İstanbul
2İstanbul Üniversitesi Cerrahpaşa Tıp Fakultesi, Tıbbi Genetik Ana Bilim Dalı, İstanbul
3İstanbul Üniversitesi Cerrahpaşa Tıp Fakultesi, İç Hastalıkları Ana Bilim Dalı, Hematoloji Bilim Dalı, İstanbul

AMAÇ: t(9;22)(q34;q11) sonucu oluşan Philadelphia (Ph) kromozomu, kronik miyeloid lösemi (KML) olgularının %90’ dan fazlasında gözlenir. KML hastalarının %5-10 unda varyant Ph translokasyonları bulunur. Varyant translokasyonlar üç ve daha fazla kromozom içerebilmektedir. Bu çalışmada varyant Ph translokasyonlu 6 KML olgusu sunulmaktadır.
YÖNTEMLER: Kemik iliği örnekleri konvansiyonel sitogenetik kullanılarak incelendi; BCR-ABL 1D problarının kullanıldığı Floresan İn Situ Hibridizasyon (FISH) yöntemi bulguların doğrulanması ve konvansiyonel sitogenetik yöntemlerinin tespit etmekte yetersiz kaldığı yeniden düzenlemelerin tanımlanması amacıyla uygulandı.
BULGULAR: Çalışmada yer alan 6 hastanın varyant Ph translokasyonları: t(7;22)(p22;q11), t(9;22;15)(q34;q11;q22), t(15;22)(p11;q11), t(1;9;22;3)(q24;q34;q11;q21), t(12;22)(p13;q11) ve t(4;8;9;22)(q11;q13;q34;q11) dır.
SONUÇ: Üç olguda basit, 3 olguda ise karmaşık (kompleks) varyant Ph translokasyonları saptamış bulunuyoruz. Olgularımızın ikisi daha önce bildirilmeyen varyant Ph kromozomları taşıyorlardı. Bu olgulardan biri klasik Ph’lı bir klonun yanısıra 1, 9, 22 ve 3 numaralı kromozomları içeren t(1;9;22;3)(q24;q34;q11;q21) formüllü yeni bir kompleks Ph translokasyonuna; diğeri ise 4, 8, 9 ve 22 numaralı kromozomları içeren t(4;8;9;22)(q11;q13;q34;q11) kompleks translokasyonlu varyant Ph’ya sahiptiler. Varyant Ph’lı 6 olgunun tümü kötü prognoza işaret eden yetersiz imatinib cevabı gösterdiler.

Anahtar Kelimeler: Kronik myeloid lösemi (KML), varyant Philadelphia kromozomu, sitogenetik, floresan in situ hibridizasyon (FISH)


Dilhan Kuru, Yelda Tarkan Argüden, Muhlis Cem Ar, Ayşe Çırakoğlu, Şeniz Öngören, Şükriye Yılmaz, Ahmet Emre Eşkazan, Ayhan Deviren, Teoman Soysal, Seniha Hacıhanefioğlu, Birsen Ülkü. Variant Philadelphia translocations with different breakpoints in six chronic myeloid leukemia patients. Turk J Hematol. 2011; 28(3): 186-192

Corresponding Author: Dilhan Kuru, Türkiye


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