Meliha NALÇACI, Ömer DEVECİOĞLU, Zafer BAŞLAR, Ayşe ÇIRAKOĞLU, Dilhan KURU, Seda EREN, Seniha HACIHANEFİOĞLU

Akut lenfoblastik lösemili hastalarda MYC gen bölgesindeki yeniden düzenlenmelerin konvansiyonel sitogenetik ve floresan in situ hibridizasyon yöntemleriyle incelenmesi

Amaç: Bu çalışmada akut lenfoblastik lösemili (ALL) hastalarda MYC gen bölgesindeki yeniden düzenlenmelerin konvansiyonel sitogenetik ve interfaz FISH yöntemleriyle incelenmesi amaçlanmıştır. Yöntemler: Çalışma, ALL tanısıyla laboratuvarımıza gönderilen 25 olgudan alınan kemik iliği örneğinde gerçekleştirildi. On dört çocukluk çağı ve 11 yetişkin ALL hastası incelendi. Konvansiyonel sitogenetik inceleme için G bantlama yöntemi, Floresan in situ hibridizasyon (FISH) yöntemi için MYC breakapart probu (Cytocell) kullanıldı.Bulgular: Toplam 25 olgunun 2'sinde (%8) değerlendirilebilecek metafaz elde edilemedi. Kromozom analizi gerçekleştirilen 23 olgunun 9'unda (%39,1) normal karyotip saptanırken, 6 olguda kromozom sayı anomalileri, 4 olguda yapı ve 4 olguda ise hem sayı hem de yapı anomalileri gözlendi. MYC gen bölgesini içine alan tek sitogenetik anomali olarak bir olguda (%4) t(8;14)(q24;q32) saptandı. Olguların tümünde FISH analizinden sonuç alındı ve 3 olguda (%12) MYC bölgesinde FISH yöntemi ile yeniden düzenlenme olduğu gösterildi. Sonuç: İki yöntem karşılaştırıldığında MYC gen bölgesinin yeniden düzenlenmelerinin gösterilmesinde FISH yönteminin daha duyarlı olduğu, ancak konvansiyonel sitogenetik yöntemlerin de kromozomlarda meydana gelen tüm değişimlerin ortaya konmasında etkili olduğu gözlendi. Bu nedenle tek bir anomali araştırılan durumlarda dahi iki yöntemin birlikte kullanımının daha etkili olacağı sonucuna varıldı

Detection of MYC gene rearrangements by conventional cytogenetics and fluorescent in situ hybridization in patients with acute lymphoblastic leukemia cases

Objective: The aim of this study is to investigate rearrangements at the region of MYC gene by conventional cytogenetics and interphase FISH methods in patients with acute lymphoblastic leukemia (ALL).Methods: The study was carried out on bone marrow specimens of 25 ALL patients who were referred to our laboratory. Fourteen children and 11 adult ALL cases were examined. Conventional cytogenetic analysis was performed using G banding technique and fluorescence in situ hybridization technique was applied using MYC breakapart probe (Cytocell).Results: Totally, in 2 of 25 cases available metaphases were not obtained. While in 9 of 23 cases were found to have normal karyotype (39.1%), numerical chromosomal abnormalities were detected in 6 cases, structural abnormalities in 4 and both numerical and structural abnormalities were found in 4 cases.In one case (4%) t(8;14)(q24;q32) was found as a cytogenetic aberration in which MYC gene locus involved. FISH analysis was performed successfully in all cases and MYC rearrangements were found in 3 cases (12%) by FISH method.Conclusion: By comparing two techniques, it was observed that FISH method showed more sensitivity, however conventional cytogenetic techniques were also effective to reveal all changes of the chromosomes. Therefore, we concluded that it would be more efficient to use of these two techniques together. J Clin Exp Invest 2015; 6 (1): 21-26

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Bassan R, Gatta G, Tondini C, Willemze R. Adult acu- te lymphoblastic leukaemia. Crit Rev Oncol Hematol 2004;50:223-261.
Başlar Z. Erişkinlerde Akut Lösemiler. Hematolog olma- yanlar için hematolojik maligniteler. İstanbul Üniversi- tesi Sürekli Tıp Eğitimi Etkinlikleri Sempozyum Dizisi 2005;45:171-180.
Harrison CJ. Acute lymphoblastic leukemia. Clin Lab Med 2011;31:631-647.
Harrison CJ, Johansson B. Acute Lymphoblastic Leu- kemia. Heim S, Mitelman F. (eds). In Cancer Cy- togenetics. 3rd edn. New Jersey: Wiley-Blackwell, 2009;233-296.
Kebriaei P, Anastasi J, Larson R.A. Acute lymphoblas- tic leukaemia: diagnosis and classification. Best Pract Res Clin Haematol 2002;15:597-621.
Faderi S, O'Brien S, Pui CH, et al. Adult acute lym- phoblastic leukemia: concepts and strategies. Cancer 2010;116:1165-1176.
Durak AB, Saydam G. Akut lenfoblastik lösemi: Sitoge- netik incelemeler ve klinik önemi. Türkiye Klinikleri J Hem Onc-Special topics 2010;3:85-91.
Boxer LM, Dang CV. Translocations involving c-myc and c-myc function. Oncogene 2001;20:5595-5610.
Delgado MD, León J. Myc roles in hematopoiesis and leukemia. Genes Cancer 2010;1:605-616.
Onciu M. Acute lymphoblastic leukemia. Hematol On- col Clin North Am 2009;23:655-674.
Soysal Y, Bahçe M, Yakıcıer M.C, et al. Lösemilerin genetik tanısında sitogenetik ve floresan in situ hibrid- izasyon yöntemlerinin etkinliğinin değerlendirilmesi. Kocatepe Tıp Dergisi 2009;10:41-47.
Shaffer L.G, McGowan-Jordan J, Schimid M (eds). ISCN(2013): An International System for Human Cy- togenetic Nomenclature. Basel: Karger, 2013;39-120.
Ventura R.A, Martin-Subero J.I, Jones M, et al. FISH analysis for the detection of lymphoma-associated chromosomal abnormalities in routine paraffin-em- bedded tissue. J Mol Diagn 2006;8:141-151.
Gmidène A, Sennana H, Elghezal H, et al. Cytoge- netic analysis of 298 newly diagnosed cases of acute lymphoblastic leukaemia in Tunisia. Hematol Oncol 2008;26:91-97.
Gil EA, Lajus TBP, de Moura TMO, et al. Banding cy- togenetic analysis in pediatric patients with acute lym- phoblastic leukemia (ALL) in a Brazilian population. Mol Cytogenetics 2013;6:37.
Mazloumi S.H.M, Madhumathi D.S, Appaji L, Prasan- nakumari. Combined Study of Cytogenetics and Fluorescence in Situ Hybridization (FISH) Analysis in Childhood Acute Lymphoblastic Leukemia (ALL) in a Tertiary Cancer Centre in South India. Asian Pac J Cancer Prev 2012;13:3825-3827.
Silva ML, Ornellas de Souza MH, Ribeiro RC, et al. Cytogenetic analysis of 100 consecutive newly diag- nosed cases of acute lymphoblastic leukemia in Rio de Janeiro. Cancer Genet Cytogenet 2002;137:85-90.
Settin A, Al Haggar M, Al Dosoky T, et al. Prognostic Cytogenetic Markers in Childhood Acute Lymphoblas- tic Leukemia. Indian J Pediatr 2007;74:255-263.
Shaikh MS, Sarwer AS, Khurshid M, Fadoo Z. Chro- mosomal abnormalities in Pakistani children with acute lymphoblastic leukemia. Asian Pac J Cancer Prev 2014;15:3907-3909.
Safaei A, Shahryari J, Farzaneh M.R, et al. Cytoge- netic findings of patients with acute lymphoblastic leu- kemia in Fars Province. Iran J Med Sci 2013;38:301- 307.
Li X, Li J, Hu J, et al. A comprehensive cytogenetic classification of 1466 Chinese patients with de novo acute lymphoblastic leukemia. Leukemia Research 2012;36:720-726.
Andreasson P, Höglund M, Békássy AN, et al. Cytoge- netic and FISH studies of a single center consecutive series of 152 childhood acute lymphoblastic leuke- mias. Eur J Haematol 2000;65:40-51.
Jarosova M, Holzerova M, Mihal V, et al. Complex karyotypes in childhood acute lymphoblastic leuke- mia: cytogenetic and molecular cytogenetic study of 21 cases. Cancer Genet Cytogenet 2003;145:161- 168.