title: KIR-HLA profiling shows presence of higher frequencies of strong inhibitory KIR-ligands among prognostically poor risk AML patients.
abstract: The expression and interaction between killer cell immunoglobulin-like receptors (KIRs) and HLA are known to be associated with pathogenesis of diseases, including hematological malignancies. Presence of B haplotype KIR in donors is associated with a lower relapse risk for acute myeloid leukemia (AML) after hematopoietic stem cell transplants (HSCT). However, the association of KIR and HLA repertoire with disease development and other clinical features is not well studied for AML. In this study, 206 Chinese patients with AML were analyzed for their FAB subtypes, risk groups, and chemo-responsiveness to assess possible association with their KIR and HLA profile. The results revealed that a B-content score of 2 was significantly more prevalent in AML patients when compared to normal controls. Notably, there is also a differential frequency in the distribution of B haplotype KIR across distinct FAB subtypes, where the M3 subtype had significantly lower frequencies of B haplotype KIR compared to the M5 subtype (p < 0.05). In addition, the stronger inhibitory KIR ligands HLA-C2 and HLA-Bw4-80I were present in significantly higher frequencies in the prognostically "poor" risk group compared to those with "favourable" risk (p < 0.01). Taken together, these associations with clinical features of AML suggest a role of the KIR-HLA repertoire in the development and biological behavior of AML.
authors.affiliation: Singapore Immunology Network, A*STAR, 8A Biomedical Grove, Immunos #03-06, Singapore, 138648, Singapore.
authors.forename: Meixin
authors.initials: M
authors.lastname: Shen
authors.affiliation: Department of Haematology, Singapore General Hospital, Academia, 20 College Road, Singapore, 169856, Singapore. linn.yeh.ching@singhealth.com.sg.
authors.forename: Yeh-Ching
authors.initials: YC
authors.lastname: Linn
authors.affiliation: Singapore Immunology Network, A*STAR, 8A Biomedical Grove, Immunos #03-06, Singapore, 138648, Singapore. ren_ee_chee@immunol.a-star.edu.sg.|Department of Microbiology, National University of Singapore, 21 Lower Kent Ridge Road, Singapore, 119077, Singapore. ren_ee_chee@immunol.a-star.edu.sg.
authors.forename: Ee-Chee
authors.initials: EC
authors.lastname: Ren
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016022:Case-Control Studies; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D008024:Ligands; D008297:Male; D008875:Middle Aged; D058889:Molecular Typing; D011379:Prognosis; D054340:Receptors, KIR / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D006680:HLA Antigens; C433932:KIR2DS2 protein, human; D008024:Ligands; D054340:Receptors, KIR
keywords: Acute myeloid leukemia; Genetic association; HLA; KIR