Maneesh Kumar Misra1, Swayam Prakash1, Nirmalya Roy Moulik2, Archana Kumar2, Suraksha Agrawal3. 1. Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, Uttar Pradesh, India. 2. Division of Pediatric Hematology-Oncology, Department of Pediatrics, King George's Medical University, Lucknow 226003, Uttar Pradesh, India. 3. Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, Uttar Pradesh, India. Electronic address: sur_ksha_agrawal@yahoo.co.in.
Abstract
BACKGROUND: Molecular interactions between KIRs and their cognate HLA class-I ligands, play a central role in the regulation of natural killer (NK) cell responses in malignancies. We aimed to determine the role of KIR genes and their HLA ligands in genetic predisposition of childhood acute lymphoblastic leukemia (ALL). METHODS: Genotyping of 16 KIR genes, along with HLA class-I groups C1/C2 and Bw4 super-type ligands, was carried-out in 137 childhood ALL cases and 274 healthy controls. RESULTS: We observed an increased incidence of activating KIRs namely; 2DS2 (OR=2.23, p=<0.001), 2DS3 (OR=1.74, p=0.011), 3DS1 (OR=2.22, p=<0.001), 2DS5 (OR=2.10, p=0.001), 2DS1 (OR=4.42, p=<0.001) and 2DS4 (OR=2.88, p=<0.001) genes in childhood ALL cases compared to controls. Frequency of BB genotype that possess 2-6 activating KIR genes was predominant in cases compared to controls (OR=2.55, p=<0.001). KIR-receptor/HLA-ligand combinations analysis revealed a moderate risk of almost 2-fold for activating KIR-ligand combinations namely; KIR2DS1-HLAC2, KIR2DS2-HLAC1 and KIR3DS1-HLABw4 in childhood ALL cases. CONCLUSION: Our data suggests the role for KIR genes and their HLA ligands in aetiology of childhood ALL.
BACKGROUND: Molecular interactions between KIRs and their cognate HLA class-I ligands, play a central role in the regulation of natural killer (NK) cell responses in malignancies. We aimed to determine the role of KIR genes and their HLA ligands in genetic predisposition of childhood acute lymphoblastic leukemia (ALL). METHODS: Genotyping of 16 KIR genes, along with HLA class-I groups C1/C2 and Bw4 super-type ligands, was carried-out in 137 childhood ALL cases and 274 healthy controls. RESULTS: We observed an increased incidence of activating KIRs namely; 2DS2 (OR=2.23, p=<0.001), 2DS3 (OR=1.74, p=0.011), 3DS1 (OR=2.22, p=<0.001), 2DS5 (OR=2.10, p=0.001), 2DS1 (OR=4.42, p=<0.001) and 2DS4 (OR=2.88, p=<0.001) genes in childhood ALL cases compared to controls. Frequency of BB genotype that possess 2-6 activating KIR genes was predominant in cases compared to controls (OR=2.55, p=<0.001). KIR-receptor/HLA-ligand combinations analysis revealed a moderate risk of almost 2-fold for activating KIR-ligand combinations namely; KIR2DS1-HLAC2, KIR2DS2-HLAC1 and KIR3DS1-HLABw4 in childhood ALL cases. CONCLUSION: Our data suggests the role for KIR genes and their HLA ligands in aetiology of childhood ALL.
Authors: Maneesh K Misra; Danillo G Augusto; Gonzalo Montero Martin; Neda Nemat-Gorgani; Jürgen Sauter; Jan A Hofmann; James A Traherne; Betsy González-Quezada; Clara Gorodezky; Will P Bultitude; Wesley Marin; Cynthia Vierra-Green; Kirsten M Anderson; Antonio Balas; Jose L Caro-Oleas; Elisa Cisneros; Francesco Colucci; Ravi Dandekar; Sally M Elfishawi; Marcelo A Fernández-Viña; Merhan Fouda; Rafael González-Fernández; Arend Große; Maria J Herrero-Mata; Sam Q Hollenbach; Steven G E Marsh; Alex Mentzer; Derek Middleton; Ashley Moffett; Miguel A Moreno-Hidalgo; Ghada I Mossallam; Annettee Nakimuli; Jorge R Oksenberg; Stephen J Oppenheimer; Peter Parham; Maria-Luiza Petzl-Erler; Dolores Planelles; Florentino Sánchez-García; Francisco Sánchez-Gordo; Alexander H Schmidt; John Trowsdale; Luciana B Vargas; Jose L Vicario; Carlos Vilches; Paul J Norman; Jill A Hollenbach Journal: Hum Immunol Date: 2018-10-12 Impact factor: 2.850
Authors: María Victoria Martínez-Sánchez; José Luis Fuster; José Antonio Campillo; Ana María Galera; Mar Bermúdez-Cortés; María Esther Llinares; Eduardo Ramos-Elbal; Juan Francisco Pascual-Gázquez; Ana María Fita; Helios Martínez-Banaclocha; José Antonio Galián; Lourdes Gimeno; Manuel Muro; Alfredo Minguela Journal: Cancers (Basel) Date: 2021-05-11 Impact factor: 6.639