Dergiler / Turkish Journal of Hematology / 2019 / Cilt: 36 - Sayı: 4

Certain Killer Immunoglobulin-Like Receptor (KIR)/KIR HLA Class I Ligand Genotypes Influence Natural Killer Antitumor Activity in Myelogenous Leukemia but Not in Acute Lymphoblastic Leukemia: A Case Control Leukemia Association Study

Bazı Öldürücü İmmünoglobulin-Benzeri Reseptör (KIR)/KIR HLA Sınıf I Ligand Genotipleri Akut Lenfoblastik Lösemide Değil ama Akut Myeloid Lösemide Doğal Öldürücü Antitümör Aktivitesini Etkilemektedir: Lösemi Birliğinin Olgu Kontrol Çalışması

Sayfa
238–246
DOI
—
🏛️Bu makalenin bibliyografik verileri ve tam metin bağlantısı DergiPark üzerinden sağlanmıştır.
DergiPark Kaydı ↗
✨

Yapay Zeka Hızlı Bakış & Çıkarımlar

AI Insight
⚡ TL;DR(1 Cümlede Hızlı Çıkarım)

Additionally, the KIR genotype characterizedby the absence of the inhibitory KIR2DL2 and the activating KIR2DS2and KIR2DS3 (ID2) was found at a lower frequency in patients compared to controls, which confirmed the need for complex analysis based onall possible KIR/HLA class I ligand polymorphism combinations.

📌 3 Maddede Bu Makale

🎯
Amaç & Hipotez:Objective: Natural killers (NK) cell function is mainly controlled bythe expression of killer immunoglobulin-like receptors (KIRs) andtheir ligation with the corresponding ligands.
📊
Temel Bulgular & Veri:The objective of thisstudy was to investigate the putative association of KIRs, HLA classI ligands, and KIR/ligand combinations with rates of development ofacute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML),and chronic myeloid leukemia (CML).Materials and Methods: The KIR/HLA I genotypes of 82 patients withleukemia (ALL, n=52; AML, n=17; and CML, n=13) were determined byPCR-SSP method and compared with genotypes of healthy controls(n=126).Results: KIR genotype frequency differed significantly betweenmyelogenous leukemia patients and healthy controls for KIR2DL5A(17.6% vs. 47.7%, p=0.02), KIR3DS1 (17.6% vs. 47.6%, p=0.02),and KIR2DS4*001 (36.6% vs. 20.2%, p=0.017).
💡
Sonuç & Katkı:Additionally, the KIR genotype characterizedby the absence of the inhibitory KIR2DL2 and the activating KIR2DS2and KIR2DS3 (ID2) was found at a lower frequency in patients compared to controls, which confirmed the need for complex analysis based onall possible KIR/HLA class I ligand polymorphism combinations.
🔬Tür:Araştırma Makalesi
📍Kapsam:Genişletilmiş Akademik Örneklem
⚙️Değişkenler:Alan Parametreleri

Özet

Objective: Natural killers (NK) cell function is mainly controlled bythe expression of killer immunoglobulin-like receptors (KIRs) andtheir ligation with the corresponding ligands. The objective of thisstudy was to investigate the putative association of KIRs, HLA classI ligands, and KIR/ligand combinations with rates of development ofacute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML),and chronic myeloid leukemia (CML).Materials and Methods: The KIR/HLA I genotypes of 82 patients withleukemia (ALL, n=52; AML, n=17; and CML, n=13) were determined byPCR-SSP method and compared with genotypes of healthy controls(n=126).Results: KIR genotype frequency differed significantly betweenmyelogenous leukemia patients and healthy controls for KIR2DL5A(17.6% vs. 47.7%, p=0.02), KIR3DS1 (17.6% vs. 47.6%, p=0.02),and KIR2DS4*001 (36.6% vs. 20.2%, p=0.017). The incidence ofhomozygous HLA-BBw4 (31.0% vs. 12.5%, p=0.042) and HLABw4Thr80 Thr80 (13.0% vs. 1.2%, p=0.01) was significantly elevatedin myeloid leukemia patients compared to healthy controls. KIR/HLAclass I ligand profile KIR3DS1(+)/L (-) was decreased and KIR3DL2(+)/HLA-A3/11(-) was increased among myeloid leukemia cases comparedto controls.Conclusion: These data suggest that the activity of NK cells asdetermined by inherited KIR/HLA class I ligand polymorphismsinfluences the susceptibility to myelogenous leukemia, but not tolymphoblastic leukemia. Additionally, the KIR genotype characterizedby the absence of the inhibitory KIR2DL2 and the activating KIR2DS2and KIR2DS3 (ID2) was found at a lower frequency in patients compared to controls, which confirmed the need for complex analysis based onall possible KIR/HLA class I ligand polymorphism combinations.

Abstract

Amaç: Doğal öldürücü (NK) hücre fonksiyonu temel olarak öldürücü immünoglobulin-benzeri reseptör (KIR) yüzey ifadesi ve bunların ilgili liganda bağlanması ile ilişkilidir. Bu çalışmanın amacı KIR, HLA sınıf I ligandlar ve KIR/ligand ilişkisinin akut lenfoblastik lösemi (ALL), akut myeloid lösemi (AML) ve kronik myeloid lösemi (KML) oluşumu ile ilişkisini araştırmaktır. Gereç ve Yöntemler: Seksen iki lösemi hastasının (ALL, n=52; AML, n=17; ve KML, n=13) KIR/HLA I genotipleri PCR-SSP metodu ile çalışıldı ve sağlıklı kontrollerin (n=126) genotipleri ile karşılaştırıldı. Bulgular: KIR genotip frekansı myeloid lösemi hastaları ve sağlıklı kontroller arasında KIR2DL5A (%17,6 vs. %47,7, p=0,02), KIR3DS1 (%17,6 vs. %47,6, p=0,02), ve KIR2DS4*001 (%36,6 vs. %20,2, p=0,017) açısından belirgin farklılık gösterdi. Homozigot HLA-BBw4 (%31,0 vs. %12,5, p=0,042) ve HLA-Bw4Thr80 Thr80 (%13,0 vs. %1,2, p=0,01) sıklığı da myeloid lösemi hastalarında sağlıklı kontrollere göre belirgin olarak daha yüksekti. Kontrollerle karşılaştırıldığında myeloid lösemi hastalarında KIR/HLA sınıf I ligand profili olarak KIR3DS1(+)/L(-) azalmış ve KIR3DL2(+)/HLA-A3/11(-) artmış olarak bulundu. Sonuç: Bu bulgular, kalıtılan KIR/HLA sınıf I ligand polimorfizmleri ile belirlenen NK hücre aktivitesinin myeloid lösemiye yatkınlığı etkilediği ancak lenfoid lösemi yatkınlığını etkilemediğini düşündürmektedir. Ayrıca inhibitor KIR2DL2, aktivatör KIR2DS2 ve KIR2DS3 (ID2) ile karakterize KIR genotipi, hastalarda kontrollere oranla daha düşük bulundu, bu da bütün olası KIR/HLA sınıf I ligand polimorfizmlerine dayanan kompleks analizlerin gerekliliğini desteklemektedir.

🔖

Bu Makaleye Atıf Yap

VARBANOVA, V., MIHAILOVA, S., NAUMOVA, E., MIHAYLOVA, A. (2019). Certain Killer Immunoglobulin-Like Receptor (KIR)/KIR HLA Class I Ligand Genotypes Influence Natural Killer Antitumor Activity in Myelogenous Leukemia but Not in Acute Lymphoblastic Leukemia: A Case Control Leukemia Association Study. Turkish Journal of Hematology, Cilt: 36 - Sayı: 4, 238–246. https://ajindex.com/articles/412723

📄 Tam Metin PDF Okuyucu

📄

PDF görüntüleyici hazırlanıyor...

Kaynakça (13)

  1. Valerianova Z, Atanasov T, Vukov M. Bulgarian National Cancer Registry. Cancer Incidence in Bulgaria, 2014 & 2015. Available at
  2. Trinchieri G. Biology of natural killer cells. Adv Immunol 1989;47:187-376
  3. Augusto DG. The impact of KIR polymorphism on the risk of developing cancer: not as strong as imagined? Front Genet 2016;7:121
  4. Parham P. MHC class I molecules and KIRs in human history, health and survival. Nat Rev Immunol 2005;5:201-214
  5. Collona M, Samaridis S. Cloning of immunoglobulin-superfamily members associated with HLA-C and HLA-B recognition by human natural killer cells. Science 1995;268:405-408
  6. Winter CC, Long EO. A single amino acid in the p58 killer cell inhibitory receptor controls the ability of natural killer cells to discriminate between the two groups of HLA-C allotypes. J Immunol 1997;158:4026-4028
  7. Cella M, Longo A, Ferrara GB, Strominger JL, Colonna M. NK3-specific natural killer cells are selectively inhibited by Bw4-positive HLA alleles with isoleucine 80. J Exp Med 1994;180:1235-1242
  8. Gumperz J, Litwin V, Philips JH, Lanier LL, Parham P. The Bw4 public epitope of HLA-B molecules confers reactivity with natural killer cell clones that express NKB1, a putative HLA receptor. J Exp Med 1995;181:1133-1144. 9.
  9. Stewart CA, Laugier-Anfossi F, Vély F, Saulquin X, Riedmuller J, Tisserant A, Gauthier L, Romagné F, Ferracci G, Arosa FA, Moretta A, Sun PD, Ugolini S, Vivier E. Recognition of peptide-MHC class I complexes by activating killer immunoglobulin-like receptors. Proc Natl Acad Sci USA 2005;102:13224- 13229
  10. Foley B, De Santis D, Lathbury L, Christiansen F, Witt C. KIR2DS1-mediated activation overrides NKG2A-mediated inhibition in HLA-C C2-negative individuals. Int Immunol 2008;20:555-563
  11. Chewning JH, Gudme CN, Hsu KC, Selvakumar A, Dupont B. KIR2DS1- positive NK cells mediate alloresponse against the C2 HLA-KIR ligand group in vitro. J Immunol 2007;179:854-868
  12. David G, Djaoud Z, Willem C, Legrand N, Rettman P, Gagne K, Cesbron A, Retière C. Large spectrum of HLA-C recognition by killer Ig-like receptor (KIR)2DL2 and KIR2DL3 and restricted C1 specificity of KIR2DS2: dominant impact of KIR2DL2/KIR2DS2 and KIR2D NK cell repertoire formation. J Immunol 2013;191:4778-4788
  13. Normam PJ, Abi-Rached L, Gendzekhadze K, Korbel D, Gleimer M, Rowley D, Bruno D, Carrington CV, Chandanayingyong D, Chang YH, Crespí C, Saruhan-Direskeneli G, Fraser PA,