Erişkin Akut Lösemilerinde İmmunhistokimyasal Pd-L1 Ve Pd-L2 Ekspresyonlarının Klinikopatolojik ve Prognostik Analizi
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Tarih
2024
Yazarlar
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Yayıncı
Necmettin Erbakan Üniversitesi, Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Erişkinlerde en sık görülen akut lösemi Akut Myeloid Lösemi (AML) olup çocuklarda ise Akut Lenfoblastik Lösemi (ALL)’dir. Refrakter ve relaps (R/R) vakalar erişkin yaş grubunda daha sık görülmektedir. Son yıllarda malign tümör insidansının artması; kemoterapi, radyoterapinin immun sistemi zayıflatması ve bu tedavilerin ciddi yan etkilere neden olmasıyla immunoterapinin önemi artmıştır. Kanser immünoterapisinde immun checkpoint moleküllerinin keşfi ise büyük atılımlara yol açmış olup solid tümörlerin tedavilerinde ve hematolojik malignitelerde ise multiple myelomda kullanılmaya başlanmıştır. Çalışmamızda Necmettin Erbakan Üniversitesi Tıp Fakültesinde 2017-2023 yıllarında 18 yaş üzerinde tanı almış ve ek hastalığı (anti PD-1/anti PD-L1 tedavisi alan non hematolojik malignite, romatolojik ve otoimmun hastalıklar) olmayan 41 ALL ve 55 AML hastasının ilk tanı aldıkları kemik iliği biyopsisi bloklarından kesitler alınarak immunhistokimyasal PD-L1 ve PD-L2 boyamaları yapıldı. Blastik hücrelerdeki PD-L1 ve PD-L2 ekspresyonlarının boyanma yüzdeleri değerlendirildi ve sonuçlar klinikopatolojik ve genetik verilerle istatistiksel olarak kıyaslandı. PD-L1 ile cinsiyet arasında erkek cinsiyet lehine zayıf korelasyon (rho:0,266, p:0,009) ve ferritin ile de pozitif yönde korelasyon (p: 0,035) saptandı. PD-L2 ekspresyonu ile lösemi tipleri arasında AML (p:0,039) yönünde, yaş (p:0,003) ve selülarite (p:0,043) ile de pozitif yönde korelasyon izlendi. Sonuç olarak çalışmamızda PD-L1 pozitifliği ALL’de %43,9, AML’de %58,2; PD-L2 pozitifliği ise ALL’de %73,1, AML de %74,5 hastada tespit edilmesi nedeniyle tedavide anti PD-1 ve anti PD-L1 ajanlarının kullanımına yer verilebileceğini ayrıca PD-L1 ekspresyonu negatif saptanan hastaların 31 (%32,2)’inde PD-L2 ekspresyonu izlenmesi nedeniyle PD-L1 negatif olgularda dahi PD-L2 pozitifliği nedeniyle anti PD-1 ajanların kullanım yolunun açılabileceğini düşünmekteyiz. Çalışmamızda PD-L1 ve PD-L2 ekspresyonunun R/R vakalarda, toplam sağ kalım ile ilişkisinde, kötü risk gruplarının ortaya konmasında anlamlı farklılık saptanmamış olup daha geniş vaka serilerinde, flow sitometri veya FISH ile değerlendirildiğinde farklı sonuçların ortaya çıkabileceğini düşünmekteyiz.
The most common acute leukemia in adults is Acute Myeloid Leukemia (AML), while in children it is Acute Lymphoblastic Leukemia (ALL). Refractory and relapsed (R/R) cases are more frequently observed in the adult age group. In recent years, the increasing incidence of malignant tumors, the immunosuppressive effects of chemotherapy and radiotherapy, and the serious side effects of these treatments have underscored the importance of immunotherapy. The discovery of immune checkpoint molecules in cancer immunotherapy has led to significant breakthroughs and has begun to be used in the treatment of solid tumors and hematologic malignancies, particularly in multiple myeloma. In our study, immunohistochemical PD-L1 and PD-L2 staining were performed on sections obtained from bone marrow biopsy blocks of 41 ALL and 55 AML patients diagnosed at Necmettin Erbakan University Faculty of Medicine between 2017 and 2023, aged 18 and older, with no comorbidities (patients receiving anti-PD-1/anti-PD-L1 treatment for non-hematologic malignancies, rheumatologic, and autoimmune diseases). The percentages of PD-L1 and PD-L2 expression in blast cells were evaluated, and the results were statistically compared with clinicopathological and genetic data. A weak correlation was found between PD-L1 positivity and male gender (rho: 0.266, p: 0.009) and a positive correlation with ferritin (p: 0.035). PD-L2 expression showed a positive correlation with leukemia types towards AML (p: 0.039), age (p: 0.003), and cellularity (p: 0.043). In conclusion, PD-L1 positivity was detected in 43.9% of ALL and 58.2% of AML patients in our study, while PD-L2 positivity was detected in 73.1% of ALL and 74.5% of AML patients. Therefore, we believe that anti-PD-1 and anti-PD-L1 agents can be incorporated into the treatment, and considering the presence of PD-L2 expression in 31 (32.2%) of patients with negative PD-L1 expression, we think that the use of anti-PD-1 agents may be considered even in cases where PD-L1 is negative due to the presence of PD-L2 positivity. In our study, no significant difference was found in the relationship between PD-L1 and PD-L2 expression in R/R cases and overall survival, or in identifying poor-risk groups. We think that different results may emerge when evaluated in larger case series, with flow cytometry or FISH.
The most common acute leukemia in adults is Acute Myeloid Leukemia (AML), while in children it is Acute Lymphoblastic Leukemia (ALL). Refractory and relapsed (R/R) cases are more frequently observed in the adult age group. In recent years, the increasing incidence of malignant tumors, the immunosuppressive effects of chemotherapy and radiotherapy, and the serious side effects of these treatments have underscored the importance of immunotherapy. The discovery of immune checkpoint molecules in cancer immunotherapy has led to significant breakthroughs and has begun to be used in the treatment of solid tumors and hematologic malignancies, particularly in multiple myeloma. In our study, immunohistochemical PD-L1 and PD-L2 staining were performed on sections obtained from bone marrow biopsy blocks of 41 ALL and 55 AML patients diagnosed at Necmettin Erbakan University Faculty of Medicine between 2017 and 2023, aged 18 and older, with no comorbidities (patients receiving anti-PD-1/anti-PD-L1 treatment for non-hematologic malignancies, rheumatologic, and autoimmune diseases). The percentages of PD-L1 and PD-L2 expression in blast cells were evaluated, and the results were statistically compared with clinicopathological and genetic data. A weak correlation was found between PD-L1 positivity and male gender (rho: 0.266, p: 0.009) and a positive correlation with ferritin (p: 0.035). PD-L2 expression showed a positive correlation with leukemia types towards AML (p: 0.039), age (p: 0.003), and cellularity (p: 0.043). In conclusion, PD-L1 positivity was detected in 43.9% of ALL and 58.2% of AML patients in our study, while PD-L2 positivity was detected in 73.1% of ALL and 74.5% of AML patients. Therefore, we believe that anti-PD-1 and anti-PD-L1 agents can be incorporated into the treatment, and considering the presence of PD-L2 expression in 31 (32.2%) of patients with negative PD-L1 expression, we think that the use of anti-PD-1 agents may be considered even in cases where PD-L1 is negative due to the presence of PD-L2 positivity. In our study, no significant difference was found in the relationship between PD-L1 and PD-L2 expression in R/R cases and overall survival, or in identifying poor-risk groups. We think that different results may emerge when evaluated in larger case series, with flow cytometry or FISH.
Açıklama
Anahtar Kelimeler
akut lösemi, acute leukemia, PD-L1, PD-L2, anti PD-1, immun kontrol noktası reseptörleri, immune checkpoint receptors, anti-PD-1
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Gürel, İ. (2024). Erişkin Akut Lösemilerinde İmmunhistokimyasal Pd-L1 Ve Pd-L2 Ekspresyonlarının Klinikopatolojik ve Prognostik Analizi. (Yayınlanmamış tıpta uzmanlık tezi) Necmettin Erbakan Üniversitesi, Tıp Fakültesi Cerrahi Tıp Bilimleri Bölümü Tıbbi Patoloji Anabilim Dalı, Konya.
