The Impact of Cytogenetic Aberrations in the Clonal Evolution of Chronic Myeloid Leukemia: A Single-Center Experience Among 450 Turkish Patients (Cohort Study)

Öz:

Objective: Chronic myeloid leukemia (CML) is a clonal hematologic disorder characterized by t(9;22) translocation, in which cytogenetic aberrations can occur in Ph(+) and (-) clones. These aberrations develop due to clonal evolution as well as treatment and they have prognostic significance. They are grouped as major and minor route anomalies in terms of their effects on prognostic parameters, such as treatment response, overall survival (OS), disease stage, complete cytogenetic response (CCyR), and major molecular response (MMR). It is stated that major route anomalies have unfavorable prognostic effects compared to minor route anomalies. We aimed to investigate the frequency and prognostic effects of cytogenetic anomalies detected in Ph(+) and (-) clones. Materials and Methods: In this study, we retrospectively analyzed the cytogenetic results of 450 patients diagnosed with CML between 2005 and 2020. Results: We detected cytogenetic aberrations in Ph-positive and negative clones in 41 of 450 patients. The most common anomalies were trisomy 8 (+8), additional Ph chromosome (+Ph), and loss of chromosome Y. Rarely, aneuploidy of the Y chromosome, dup (22), +11, and +6 were seen in CML patients. We observed that these identified aberrations negatively affected MMR and CCyR, and generally resulted in changing imatinib treatment for second-generation tyrosine kinase activity inhibitors. Our results are compatible with the literature.Conclusion: We suggest that cytogenetic aberrations detected in Ph(+) and (-) clones should be a warning sign in terms of treatment and require close observation. The use of cytogenetic methods for the identification of these anomalies is also important.

Anahtar Kelime:

Kronik Myeloid Löseminin Klonal Evolüsyonunda Sitogenetik Aberasyonların Etkisi: 450 Türk Hastadan Oluşan Kohort Çalışmasında Tek Merkez Deneyimi

Öz:

Amaç: Kronik myeloid lösemi (KML), t(9;22) ile karakterize olan, Ph(+) ve (-) klonlarda sitogenetik aberasyonların gelişebildiği bir lösemi tipi olarak bilinmektedir. Bu aberasyonlar klonal evolüsyon ve tedaviye bağlı gelişmekte olup, prognostik etkileri olduğu bilinmektedir. Literatürde; tedavi yanıtı, toplam sağkalım (OS), hastalık evresi, tam sitogenetik yanıt (TSY) ve majör moleküler yanıt (MMY) gibi prognostik parametreler üzerine olan etkileri açısından bu anomaliler majör ve minör yolak anomalileri olarak gruplandırılmaktadır. Majör yolak anomalilerinin minör yolak anomalilerine göre prognozu olumsuz yönde etkilediği belirtilmektedir. Biz de, Ph(+) ve (-) klonda saptanan sitogenetik anomalilerin sıklığını ve prognostik etkisini araştırmayı amaçladık. Gereç ve Yöntemler: Bu çalışmada, 2005-2020 yılları arasında KML tanısı almış 450 hastanın retrospektif olarak sitogenetik sonuçlarını inceledik. Bulgular: Bu hastaların 41/450’ inde Ph(+) ve/veya (-) klonda sitogenetik aberasyonlar saptadık. En sık gözlenen anomaliler trizomi 8 (+8), ek Ph kromozomu (+Ph) ve Y kromozom kaybı idi. Ayrıca KML hastalarında nadir görülen dup (22), +11, +6 ve Y kromozom artışı; ve daha önce literatürde saptanmayan inv(1) anomalisini tespit ettik. Saptanan bu aberasyonların MMY ve TSY olumsuz etkilediğini ve tedavide de genellikle 2. nesil tirozin kinaz aktivite inhibitörlerin tercih edildiğini gözledik. Elde ettiğimiz sonuçlar, literatür verileri ile uyumluluk göstermektedir. Sonuç: Sonuç olarak, Ph(+) ve (-) klonda saptanan sitogenetik aberasyonların hastaların tedavisi ve yakın takibi için “uyarı” niteliği taşıdığını savunmaktayız. Ayrıca bu kromozomal anomalilerin saptanması açısından sitogenetik yöntemlerin öneminin yadsınamaz olduğunu düşünmekteyiz.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

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APA	IŞIK S, günden g, Üsküdar Teke H, akay o, Oguz Davutoglu N, Aslan V, KARAGÜLLE M, Ozen H, ÇILINGIR O, Artan S, durak aras b (2022). The Impact of Cytogenetic Aberrations in the Clonal Evolution of Chronic Myeloid Leukemia: A Single-Center Experience Among 450 Turkish Patients (Cohort Study). , 237 - 244. 10.4274/tjh.galenos.2022.2022.0045
Chicago	IŞIK SEVGİ,günden gülçin,Üsküdar Teke Hava,akay olga meltem,Oguz Davutoglu Nur,Aslan Vahap,KARAGÜLLE Mustafa,Ozen Hulya,ÇILINGIR OGUZ,Artan Sevilhan,durak aras beyhan The Impact of Cytogenetic Aberrations in the Clonal Evolution of Chronic Myeloid Leukemia: A Single-Center Experience Among 450 Turkish Patients (Cohort Study). (2022): 237 - 244. 10.4274/tjh.galenos.2022.2022.0045
MLA	IŞIK SEVGİ,günden gülçin,Üsküdar Teke Hava,akay olga meltem,Oguz Davutoglu Nur,Aslan Vahap,KARAGÜLLE Mustafa,Ozen Hulya,ÇILINGIR OGUZ,Artan Sevilhan,durak aras beyhan The Impact of Cytogenetic Aberrations in the Clonal Evolution of Chronic Myeloid Leukemia: A Single-Center Experience Among 450 Turkish Patients (Cohort Study). , 2022, ss.237 - 244. 10.4274/tjh.galenos.2022.2022.0045
AMA	IŞIK S,günden g,Üsküdar Teke H,akay o,Oguz Davutoglu N,Aslan V,KARAGÜLLE M,Ozen H,ÇILINGIR O,Artan S,durak aras b The Impact of Cytogenetic Aberrations in the Clonal Evolution of Chronic Myeloid Leukemia: A Single-Center Experience Among 450 Turkish Patients (Cohort Study). . 2022; 237 - 244. 10.4274/tjh.galenos.2022.2022.0045
Vancouver	IŞIK S,günden g,Üsküdar Teke H,akay o,Oguz Davutoglu N,Aslan V,KARAGÜLLE M,Ozen H,ÇILINGIR O,Artan S,durak aras b The Impact of Cytogenetic Aberrations in the Clonal Evolution of Chronic Myeloid Leukemia: A Single-Center Experience Among 450 Turkish Patients (Cohort Study). . 2022; 237 - 244. 10.4274/tjh.galenos.2022.2022.0045
IEEE	IŞIK S,günden g,Üsküdar Teke H,akay o,Oguz Davutoglu N,Aslan V,KARAGÜLLE M,Ozen H,ÇILINGIR O,Artan S,durak aras b "The Impact of Cytogenetic Aberrations in the Clonal Evolution of Chronic Myeloid Leukemia: A Single-Center Experience Among 450 Turkish Patients (Cohort Study)." , ss.237 - 244, 2022. 10.4274/tjh.galenos.2022.2022.0045
ISNAD	IŞIK, SEVGİ vd. "The Impact of Cytogenetic Aberrations in the Clonal Evolution of Chronic Myeloid Leukemia: A Single-Center Experience Among 450 Turkish Patients (Cohort Study)". (2022), 237-244. https://doi.org/10.4274/tjh.galenos.2022.2022.0045

APA	IŞIK S, günden g, Üsküdar Teke H, akay o, Oguz Davutoglu N, Aslan V, KARAGÜLLE M, Ozen H, ÇILINGIR O, Artan S, durak aras b (2022). The Impact of Cytogenetic Aberrations in the Clonal Evolution of Chronic Myeloid Leukemia: A Single-Center Experience Among 450 Turkish Patients (Cohort Study). Turkish Journal of Hematology, 39(4), 237 - 244. 10.4274/tjh.galenos.2022.2022.0045
Chicago	IŞIK SEVGİ,günden gülçin,Üsküdar Teke Hava,akay olga meltem,Oguz Davutoglu Nur,Aslan Vahap,KARAGÜLLE Mustafa,Ozen Hulya,ÇILINGIR OGUZ,Artan Sevilhan,durak aras beyhan The Impact of Cytogenetic Aberrations in the Clonal Evolution of Chronic Myeloid Leukemia: A Single-Center Experience Among 450 Turkish Patients (Cohort Study). Turkish Journal of Hematology 39, no.4 (2022): 237 - 244. 10.4274/tjh.galenos.2022.2022.0045
MLA	IŞIK SEVGİ,günden gülçin,Üsküdar Teke Hava,akay olga meltem,Oguz Davutoglu Nur,Aslan Vahap,KARAGÜLLE Mustafa,Ozen Hulya,ÇILINGIR OGUZ,Artan Sevilhan,durak aras beyhan The Impact of Cytogenetic Aberrations in the Clonal Evolution of Chronic Myeloid Leukemia: A Single-Center Experience Among 450 Turkish Patients (Cohort Study). Turkish Journal of Hematology, vol.39, no.4, 2022, ss.237 - 244. 10.4274/tjh.galenos.2022.2022.0045
AMA	IŞIK S,günden g,Üsküdar Teke H,akay o,Oguz Davutoglu N,Aslan V,KARAGÜLLE M,Ozen H,ÇILINGIR O,Artan S,durak aras b The Impact of Cytogenetic Aberrations in the Clonal Evolution of Chronic Myeloid Leukemia: A Single-Center Experience Among 450 Turkish Patients (Cohort Study). Turkish Journal of Hematology. 2022; 39(4): 237 - 244. 10.4274/tjh.galenos.2022.2022.0045
Vancouver	IŞIK S,günden g,Üsküdar Teke H,akay o,Oguz Davutoglu N,Aslan V,KARAGÜLLE M,Ozen H,ÇILINGIR O,Artan S,durak aras b The Impact of Cytogenetic Aberrations in the Clonal Evolution of Chronic Myeloid Leukemia: A Single-Center Experience Among 450 Turkish Patients (Cohort Study). Turkish Journal of Hematology. 2022; 39(4): 237 - 244. 10.4274/tjh.galenos.2022.2022.0045
IEEE	IŞIK S,günden g,Üsküdar Teke H,akay o,Oguz Davutoglu N,Aslan V,KARAGÜLLE M,Ozen H,ÇILINGIR O,Artan S,durak aras b "The Impact of Cytogenetic Aberrations in the Clonal Evolution of Chronic Myeloid Leukemia: A Single-Center Experience Among 450 Turkish Patients (Cohort Study)." Turkish Journal of Hematology, 39, ss.237 - 244, 2022. 10.4274/tjh.galenos.2022.2022.0045
ISNAD	IŞIK, SEVGİ vd. "The Impact of Cytogenetic Aberrations in the Clonal Evolution of Chronic Myeloid Leukemia: A Single-Center Experience Among 450 Turkish Patients (Cohort Study)". Turkish Journal of Hematology 39/4 (2022), 237-244. https://doi.org/10.4274/tjh.galenos.2022.2022.0045