The Prognostic Significance of Serum Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) in Childhood Acute Leukemias
Öz
Purpose: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a TNF superfamily member. TRAIL is transmembrane protein expressed on cell surfaces and has a broad expression pattern in a variety of organs. Cleavage of its C-terminal part (extracellular domain) allows for a soluble form of TRAIL.TRAIL induces apoptosis with its receptors TRAIL-receptor 1 (TRAIL-R1), TRAIL-receptor 2 (TRAIL-R2) however apoptosis can not be induced by receptors TRAIL-receptor 3 (TRAIL-R3) and TRAIL-receptor 4 (TRAIL-R4). There are many trials to search the correlation between leukemia and apoptotic pathway disorders. In this study we determined the seum levels of TRAIL in acute childhood leukemias at first diagnose. We aimed to determine the relation between the levels of serum TRAIL and patient’s survey, clinical parameters. Material and Methods: The study was performed in patients admitted to Pediatric Hematology and Pediatric Oncology Department of Çukurova University Medical Faculty between October 2009 and July 2010. Twenty-three cases with new diagnosis acute lymphoblastic leukemia (ALL) at the age disturbition 9-months-12-year and 8-months and fourteen cases with new diagnosis acute myeloblastic leukemia (AML) at the age disturbition of 9 days-18 years are included in this study. Twenty-one healty children with no blood disease with similar sex and age with leukemia group was chosen as the control group. Serum TRAIL levels were determined by using ELISA method. Results: The comparison of the average values of the TRAIL levels in acute leukemia patients and control group have shown that patients with leukemia have low serum TRAIL levels (p=0.002). In patients with high-risk-grade (HRG) of ALL compared with control group have shown low serum TRAIL levels in HRG of ALL (p=0.008). In patients with common acute lymphoblastic leukemia antigen(CALLA)(- ) B ALL compared with control group have shown low serum TRAIL levels in CALLA(-) B ALL (p=0.004). Children with acute leukemias (ALL, AML) who died during treatment compared with survived group have shown low levels of serum TRAIL in expired patients (p=0.004). Conclusion: As a result, serum TRAIL might play a role in leukomegenesis. The low levels of serum TRAIL detected in our patients may be associated with leukomogenezis and impaired TRAIL-mediated apoptosis. To suggest soluble TRAIL’s role in acute leukemias detection of TRAIL-mediated apoptosis is needed. The low serum TRAIL may be used as a sign of bad prognosis. For more comphrensive results prospective studies with greaater number of patients are needed.
Anahtar Kelimeler
Kaynakça
- Margolin JF, Steuber CP, Poplack DG (editors). Acute Lymphoblastic Leukemia. In: Principles and Practice of Pediatric Oncology, 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2002;489-544.
- Schuler D, Szende B. Apoptosis in acute leukemia. Leuk Res. 2004;28:661-6.
- Ugo T. TRAIL/TRAIL-R in hematologic malignencies. J Cell Biochem. 2010;110:21-34.
- Hengartner MO. Death cycle and Swiss army knives. Nature. 1998;391:441-2. Soluble form of TRAIL, Fas, and FasL in the serum of patients with B-CLL. Rocz Akad Med Bialymst. 2005; 50:204-7.
- Tanaka H, Ito T, Kyo T, Kimura A. Treatment with IFNα in vivo up-regulates serum-soluble TNF-related apoptosis inducing ligand (sTRAIL) levels and TRAIL mRNA expressions in neutrophils in chronic myelogenous leukemia patients. Eur J Haematol. 2007; 78: 389-98.
- Mirandola P, Ponti C, Gobbi G, Vaccarezza M. Activated human NK and CD8+ T cells Express both TNF-related apoptosis-inducing ligand (TRAIL) and TRAIL receptors but are resistant to TRAIL- mediated cytotoxicity. Blood. 2004; 104: 2418-24.
- Clodi K, Wimmer D, Li Y, Goodwin R, Jaeger U, Mann G, Gadner H, Younes A. Exspression of tumor necrosis factor (TNF)-related apoptosis inducing ligand(TRAIL) receptors and sensivity of TRAIL induced apoptosis in primaryB-cell acute lymphoblastic leukemia cells. Br J Haematol. 2000;111:580-6.
- Zaho A, Wang Y, Goodwin R, Andreeff M, Younes A. Functional expression of TRAIL by lymphoid and myeloid tumor cells. Br J Haematol. 1999;106:827- 32.
- Jimenez-Lara AM, Clarke N, Altucci L, Gronemever H. Retinoic-acid-induced apoptosis in leukemia cells. Trends Mol Med. 2004;10:508-15.
Çocukluk Çağı Akut Lösemilerinde Serum Tümör Nekroze Edici Faktör (TNF) İlişkili Apopitoz İndükleyici Proteinin (TRAIL) Prognostik Önemi
Öz
Amaç: Tümör nekroze edici faktör(TNF) ilişkili apopitoz indükleyici protein (TRAIL) TNF süper ailesinin bir üyesidir. TRAIL pek çok organda ekprese edilen, hücre yüzeyinde yer alan transmembran bir proteindir. C-domainin (hücre dışında yer alan)ayrılması sonucunda serumda bulunan formunun oluşmasına izin verir.TRAIL, reseptörlerinden TRAIL reseptör 1 (TRAIL-R1) ve TRAIL reseptör 2 (TRAIL-R2)' ye bağlanarak apopitozu indükler bununla birlikte apopitoz sinyali TRAIL reseptör 3 (TRAIL-R3) ve TRAIL reseptör 4 (TRAIL-R4) ile bağlanması sonucunda indüklenemez. Apopitotik yolak bozuklukları ve lösemi gelişimi arasındaki ilişkiyi araştıran pek çok çalışma yapılmıştır.Çalışmamızda akut lösemi hastalarında ilk tanı anında serum TRAIL miktarını tespit etmek istedik. Serum TRAIL'ın akut lösemi hastalarında hasta sağkalımı ve klinik parametrelerle ilişkisini incelemeyi amaçladık. Materyal ve Metod: Bu çalışma Ekim 2009– Temmuz 2010 tarihleri arasında Çukurova Üniversitesi Tıp Fakültesi Çocuk Hematoloji ve Çocuk Onkoloji Bilim Dalına başvuran hastalarda yapıldı. Çalışmaya 9 ay-12 yaş 8ay yaş dağılımında yeni tanı almış 23 akut lenfoblastik lösemili (ALL) hasta ile, 9 gün-19 yaş dağılımında yeni tanı almış 14 akut miyeloblastik lösemili (AML) hasta dahil edildi. Sağlıklı, kan hastalığı olmayan, lösemi grubuna benzer yaş ve cinsiyetteki 21 çocuk, kontrol grubu olarak seçildi. Serum TRAIL düzeyleri Elisa yöntemi ile araştırıldı. Bulgular: Akut lösemi tanılı hastalar ile kontrol grubu karşılaştırıldığında akut lösemi hastalarında ortalama serum TRAIL düzeyi sağlıklı kontrollerden düşük tespit edildi (p=0,002). ALL’li yüksek risk grubundaki (HRG) hastalarda, TRAIL düzeyi kontrol grubuna göre düşük tespit edildi (p=0,008). Common akut lenfoblastik lösemi antijeni (CALLA )(-) B ALL grubunda TRAIL düzeyi kontrol grubuna göre düşük tespit edildi (p=0,004). Lösemi tanısı alan ve eksitus olan hastalarla yaşayan hastalar kıyaslandığında TRAIL düzeyi eksitus olan grupta düşük tespit edildi (p=0,004). Sonuç: Serum TRAIL lösemi hastalarında lökomogenezde rol oynayabilir. Hastalarımızda tespit edilen düşük serum TRAIL düzeyleri azalmış TRAIL aracılıklı apopitoza ve lökomogeneze neden olmuş olabilir. Akut lösemi patogenezinde serum TRAIL'ın rol aldığını önermek için eş zamanlı bakılmış TRAIL aracılıklı apopitotik aktivitenin ölçülmesi gereklidir.Düşük serum TRAIL düzeyi kötü prognozu gösteren bir belirteç olarak kullanılabilir. Daha kapsamlı sonuçlar elde etmek için daha çok sayıda vaka ile yapılmış prospektif çalışmalara ihtiyaç vardır.
Anahtar Kelimeler
Kaynakça
- Margolin JF, Steuber CP, Poplack DG (editors). Acute Lymphoblastic Leukemia. In: Principles and Practice of Pediatric Oncology, 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2002;489-544.
- Schuler D, Szende B. Apoptosis in acute leukemia. Leuk Res. 2004;28:661-6.
- Ugo T. TRAIL/TRAIL-R in hematologic malignencies. J Cell Biochem. 2010;110:21-34.
- Hengartner MO. Death cycle and Swiss army knives. Nature. 1998;391:441-2. Soluble form of TRAIL, Fas, and FasL in the serum of patients with B-CLL. Rocz Akad Med Bialymst. 2005; 50:204-7.
- Tanaka H, Ito T, Kyo T, Kimura A. Treatment with IFNα in vivo up-regulates serum-soluble TNF-related apoptosis inducing ligand (sTRAIL) levels and TRAIL mRNA expressions in neutrophils in chronic myelogenous leukemia patients. Eur J Haematol. 2007; 78: 389-98.
- Mirandola P, Ponti C, Gobbi G, Vaccarezza M. Activated human NK and CD8+ T cells Express both TNF-related apoptosis-inducing ligand (TRAIL) and TRAIL receptors but are resistant to TRAIL- mediated cytotoxicity. Blood. 2004; 104: 2418-24.
- Clodi K, Wimmer D, Li Y, Goodwin R, Jaeger U, Mann G, Gadner H, Younes A. Exspression of tumor necrosis factor (TNF)-related apoptosis inducing ligand(TRAIL) receptors and sensivity of TRAIL induced apoptosis in primaryB-cell acute lymphoblastic leukemia cells. Br J Haematol. 2000;111:580-6.
- Zaho A, Wang Y, Goodwin R, Andreeff M, Younes A. Functional expression of TRAIL by lymphoid and myeloid tumor cells. Br J Haematol. 1999;106:827- 32.
- Jimenez-Lara AM, Clarke N, Altucci L, Gronemever H. Retinoic-acid-induced apoptosis in leukemia cells. Trends Mol Med. 2004;10:508-15.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Bölüm | Araştırma |
| Yazarlar | |
| Yayımlanma Tarihi | 2 Ekim 2015 |
| Yayımlandığı Sayı | Yıl 2015 Cilt: 40 Sayı: 4 |
