Ayşe Pınar ERÇETİN, Safiye AKTAŞ, Özden PİŞKİN, Mehmet Ali ÖZCAN

Multipl miyelomda galektin-1 ekspresyonunun düzenleyici T hücreler ve otolog kemik iliği transplantasyonu ile ilişkisi

Amaç: Multipl Miyelom (MM), plazma hücrelerinin ve plazma hücresi öncülerinin malign proliferasyonu ile karakterize olan bir hematolojik kanserdir. Düzenleyici T hücreler (Treg) organizmanın kendisine ait ve yabancı antijenlere karşı verdiği immün yanıtı kontrol ederek, immünite ve tolerans arasındaki dengeyi sağlamaktadırlar. Immünsüpresif CD4+CD25+FOXP3+ Tregler MM’de yüksek düzeylerde görülmektedir. Galektin-1 (Gal-1) hücre gelişiminin inhibisyonunu indüklemekte ve dinlenme halinde olmayan, aktif immün hücrelerin apoptozunu ilerletir ve aktivasyonun ardından Treglerde aşırı ekspresyonu görülmektedir. Bu çalışmanın amacı MM’de Gal- 1 ekspresyonunun CD4+CD25+Foxp3+ Treg hücreler ve Otolog Kemik İliği Transplantasyonu (OKİT) ile ilişkisini araştırmaktır. Gereç ve Yöntem: Periferik kan örnekleri 19 MM hastasından toplanıp OKİT varlığına göre iki grup olarak alt sınıflandırıldı. Periferik Kan Mononükleer Hücreleri (PKMH) Biocoll solüsyonunda yoğunluk gradiyenti santrifüjü ile izole edilip Tregler için hemen akım sitometri analizi yapıldı. Gal-1 ekspresyonu PKMH yaymalarında immünositokimya ile tespit edilerek semikantitatif olarak düşük, orta ve yüksek ifadeleri ile değerlendirildi. Bulgular nonparametrik testler ile istatistiksel olarak analiz edildi. Bulgular: Bu çalışma 7 tanesi OKİT (+) olan toplam 19 MM hastası içermektedir. Gal-1 ekspresyonu olguların %52,6’sında orta veya yüksek olarak saptanmıştır. CD4+CD25+Foxp3+ Tregler miktarı OKİT (+) grupta daha yüksek bulunmuştur. Treg yüzdeleri ve Gal-1 ekspresyonu istatistiksel anlamlı bir ilişki (p>0,05) göstermemiştir. Buna ek olarak Gal-1 ekspresyonu OKİT varlığı ya da prognoz (p>0,05) ile de istatistiksel anlamlılık göstermemiştir. Sonuç: Bu çalışma ile Gal-1 ekspresyonu MM’da PKMH’lerinde Tregler, OKİT ve prognoz ile ilişkisi açısından ilk defa sorgulanmıştır. Gal-1 ekspresyonu ile Tregler, OKİT ve prognoz arasında hiçbir istatistiksel anlamlı ilişki saptanmamıştır. Sınırlı sayıda olgu bulunması bu duruma neden olmuş olabilir. Bundan sonraki adımımız Gal-1’in MM ‘da kemik iliğindeki ekspresyon düzeyini ortaya koymak olabilir.

Galectin-1 expression in multiple myeloma in relation with T regulatory cells and autologous bone marrow transplantation

Objective: Multiple Myeloma (MM) is a hematological cancer which is characterized with malignant proliferation of plasma cells and their precursors. Regulatory T cells (Tregs) control immune responses to self-and foreign-antigens and maintain the balance between immunity and tolerance. Immunosuppressive CD4+CD25+FOXP3+ Tregs shows high levels in MM. Galectin-1 (Gal-1) induces the inhibition of cell growth and promotes the apoptosis of activated, not resting, immune cells and it is overexpressed in Tregs after activation. The aim of this study is to determine Gal-1 expression in MM and its relation with CD4+CD25+Foxp3+ Tregs levels and autologous bone marrow transplantation (ABMT). Material and Method: Peripheral blood samples were collected from 19 MM patients and sub-classified into two groups according to presence of ABMT. Peripheral blood mononuclear cells (PBMCs) were isolated by density gradient centifugation on Biocoll solution and underwent immediate analysis by flow cytometry for Tregs. Gal-1 was determined by immunocytochemistry on imprints of PBMCs and scored as low, medium and high expression semiquantitatively. Results were statististically analyzed by nonparametric tests. Results: This study included 19 MM patients and 7 of them were ABMT (+). Moderate or high levels of Gal-1 expression were detected in 52.6 % of all cases. CD4+CD25+Foxp3+ Tregs were shown to be higher in ABMT (+). Tregs percentage and Gal-1 expression did not show statistical significance (p>0.05). In addition Gal-1 expression did not show statistical significance with ABMT presence or prognosis (p>0.05). Conclusion: In this study Gal-1 expression in PBMCs was the first time questioned for the relation of Tregs, ABMT and prognosis in MM. Gal-1 did not show statistical relation with any. Limited number of cases might be the reason. Our next step shall be determining its expression in bone marrow.

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