Notch Expression Level in Chronic Lymphocytic Leukemia Patients: Evaluation by Flow Cytometry

Fatma Betul Oktelık; Murat Özbalak; İpek Yönal Hindilerden; Günnur Deniz; Metin Yusuf Gelmez

Makale detayları

Notch Expression Level in Chronic Lymphocytic Leukemia Patients: Evaluation by Flow Cytometry

Yazarlar:

Fatma Betul Oktelık | Murat Özbalak | İpek Yönal Hindilerden | Günnur Deniz | Metin Yusuf Gelmez

Yayıncı:

Kocaeli University

Ana Başlıklar:

İmmünoloji (Diğer) | Hematoloji

Dergi:

Acta Medica Nicomedia Vol.8 Issue 2, pp.140-145

Belge Tipi:

Makale

Yayın Tarihi:

6/2025

Belge Dili:

Türkçe

Document ID (Org No.):

2001353776

pISSN:

2717-8994

Anahtar kelimeler:

Özet:

 Objective: Chronic lymphocytic leukemia CLL, characterized by the accumulation of CD5CD19 malignant B cells in the bone marrow and blood, is the most common type of leukemia in adults in Western countries. While CD38 and ZAP70 expression and immunoglobulin heavy chain variable region IgVH mutations provide insights into the clinical outcome of the disease, the pathogenesis of CLL has not yet been fully elucidated. Notch receptors, which are transmembrane proteins, play a critical role in regulating cell proliferation, differentiation, and apoptosis. Recent studies have demonstrated the involvement of Notch proteins in various types of cancer. It has been reported that 10 of CLL patients had Notch1 mutations, and this mutation is associated with poorer prognosis. In this study, the levels of Notch molecules were analyzed in CLL patients to investigate their roles in the pathogenesis of the disease. Methods: Notch-1, Notch2, Notch3, and Notch4 levels were analyzed by flow cytometry in peripheral blood mononuclear cells isolated from heparinized blood samples of 15 CLL patients and 9 healthy individuals. Results: Compared to healthy individuals, increased Notch1and decreased Notch4 levels were found in total lymphocytes, B cells, and T lymphocytes in CLL patients. No significant differences were detected in Notch2 and Notch3 expression between patients and healthy individuals. Conclusion: Recent studies showed that Notch1enhances cell survival and increases resistance to apoptosis. Additionally, increased Notch1mRNA expression has been reported in CLL patients, which may be associated with a poorer disease prognosis. This study, through flow cytometry analysis, demonstrated elevated Notch1protein levels, suggesting that Notch1could be a potential new biomarker involved in the pathogenesis of CLL.

 Objective: Chronic lymphocytic leukemia CLL, characterized by the accumulation of CD5CD19 malignant B cells in the bone marrow and blood, is the most common type of leukemia in adults in Western countries. While CD38 and ZAP70 expression and immunoglobulin heavy chain variable region IgVH mutations provide insights into the clinical outcome of the disease, the pathogenesis of CLL has not yet been fully elucidated. Notch receptors, which are transmembrane proteins, play a critical role in regulating cell proliferation, differentiation, and apoptosis. Recent studies have demonstrated the involvement of Notch proteins in various types of cancer. It has been reported that 10 of CLL patients had Notch1 mutations, and this mutation is associated with poorer prognosis. In this study, the levels of Notch molecules were analyzed in CLL patients to investigate their roles in the pathogenesis of the disease. Methods: Notch-1, Notch2, Notch3, and Notch4 levels were analyzed by flow cytometry in peripheral blood mononuclear cells isolated from heparinized blood samples of 15 CLL patients and 9 healthy individuals. Results: Compared to healthy individuals, increased Notch1and decreased Notch4 levels were found in total lymphocytes, B cells, and T lymphocytes in CLL patients. No significant differences were detected in Notch2 and Notch3 expression between patients and healthy individuals. Conclusion: Recent studies showed that Notch1enhances cell survival and increases resistance to apoptosis. Additionally, increased Notch1mRNA expression has been reported in CLL patients, which may be associated with a poorer disease prognosis. This study, through flow cytometry analysis, demonstrated elevated Notch1protein levels, suggesting that Notch1could be a potential new biomarker involved in the pathogenesis of CLL.

 Objective: Chronic lymphocytic leukemia CLL, characterized by the accumulation of CD5CD19 malignant B cells in the bone marrow and blood, is the most common type of leukemia in adults in Western countries. While CD38 and ZAP70 expression and immunoglobulin heavy chain variable region IgVH mutations provide insights into the clinical outcome of the disease, the pathogenesis of CLL has not yet been fully elucidated. Notch receptors, which are transmembrane proteins, play a critical role in regulating cell proliferation, differentiation, and apoptosis. Recent studies have demonstrated the involvement of Notch proteins in various types of cancer. It has been reported that 10 of CLL patients had Notch1 mutations, and this mutation is associated with poorer prognosis. In this study, the levels of Notch molecules were analyzed in CLL patients to investigate their roles in the pathogenesis of the disease. Methods: Notch-1, Notch2, Notch3, and Notch4 levels were analyzed by flow cytometry in peripheral blood mononuclear cells isolated from heparinized blood samples of 15 CLL patients and 9 healthy individuals. Results: Compared to healthy individuals, increased Notch1and decreased Notch4 levels were found in total lymphocytes, B cells, and T lymphocytes in CLL patients. No significant differences were detected in Notch2 and Notch3 expression between patients and healthy individuals. Conclusion: Recent studies showed that Notch1enhances cell survival and increases resistance to apoptosis. Additionally, increased Notch1mRNA expression has been reported in CLL patients, which may be associated with a poorer disease prognosis. This study, through flow cytometry analysis, demonstrated elevated Notch1protein levels, suggesting that Notch1could be a potential new biomarker involved in the pathogenesis of CLL.

 Amaç: CD5CD19 malign B hücrelerin kemik iliği ve kanda birikmesi ile karakterize kronik lenfositik lösemi KLL, Amerika ve Avrupada yetişkinlerde en sık gözlenen lösemi tipidir. CD38, ZAP70 ekspresyonları, immünoglobülin ağır zincir değişken bölge IgVH mutasyonları hastalığın klinik seyri hakkında bilgi sağlasa da KLL patogenezi henüz net olarak tanımlanmamıştır. Transmembran proteini olan Notch reseptörleri hücre çoğalması, farklılaşması ve apoptozis süreçlerinde immün homeostazın sağlanmasında oldukça önemlidir. Güncel çalışmalar, Notch moleküllerinin kanser gelişiminde rolü olduğunu göstemektedir. Bu çalışmada KLL tanısı almış hastalarda Notch seviyeleri analiz edilerek KLL patogenezindeki rolleri incelenmiştir. Yöntem: KLL tanılı 15 hasta ve 9 sağlıklı bireyin periferik kanından izole edilen periferik kan mononükleer hücrelerde akan hücre ölçer ile Notch1, Notch2, Notch3 ve Notch4 seviyeleri değerlendirildi. Bulgular: KLL hastalarında lenfosit, CD19 B ve CD3 T hücrelerde Notch1 ifadesinin arttığı, buna karşın Notch4 ifadesinin ise azaldığı gözlendi. Hasta ve sağlıklı bireyler arasında Notch2 ve Notch3 ifadeleri arasında anlamlı fark gözlenmedi. Sonuç: Notch1hücreleri apoptoza karşı dirençli hale getirerek hücre sağ kalımı üzerine pozitif etkide bulunmaktadır. KLL hastalarında Notch1 gen ifadesinin yükseldiği ve kötü prognoz ile ilişkili olduğu bildirilmektedir. Bulgularımız akan hücre ölçer ile Notch ifadelerinin hastalarda hızlı bir şekilde değerlendirilebileceğini ve değişen Notch1 ve Notch4 ifadelerinin KLL patogenezinde incelenmesi gereken potansiyel belirteçler olarak öne çıkabileceğini göstermektedir.

Makale detayları

Notch Expression Level in Chronic Lymphocytic Leukemia Patients: Evaluation by Flow Cytometry

Yazarlar:

Fatma Betul Oktelık | Murat Özbalak | İpek Yönal Hindilerden | Günnur Deniz | Metin Yusuf Gelmez

Yayıncı:

Kocaeli University

Ana Başlıklar:

İmmünoloji (Diğer) | Hematoloji

Dergi:

Acta Medica Nicomedia Vol.8 Issue 2, pp.140-145

Belge Tipi:

Makale

Yayın Tarihi:

6/2025

Belge Dili:

Türkçe

Document ID (Org No.):

2001353776

pISSN:

2717-8994

Chronic lymphocytic leukemia

Notch1

Notch2

Notch3

Notch4Kronik lenfositik lösemi

Notch1

Notch2

Notch3

Notch4

Sayı

Makale detayları

Yazarlar: Fatma Betul Oktelık | Murat Özbalak | İpek Yönal Hindilerden | Günnur Deniz | Metin Yusuf Gelmez

Yayıncı: Kocaeli University

Ana Başlıklar: İmmünoloji (Diğer) | Hematoloji

Dergi: Acta Medica Nicomedia Vol.8 Issue 2, pp.140-145

Belge Tipi: Makale

Yayın Tarihi: 6/2025

Belge Dili: Türkçe

Document ID (Org No.): 2001353776

pISSN: 2717-8994

Sayı

Yazarlar:

Fatma Betul Oktelık | Murat Özbalak | İpek Yönal Hindilerden | Günnur Deniz | Metin Yusuf Gelmez

Yayıncı:

Kocaeli University

Ana Başlıklar:

İmmünoloji (Diğer) | Hematoloji

Dergi:

Acta Medica Nicomedia Vol.8 Issue 2, pp.140-145

Belge Tipi:

Makale

Yayın Tarihi:

6/2025

Belge Dili:

Türkçe

Document ID (Org No.):

2001353776

pISSN:

2717-8994