A Novel Hypothesis: Certain KIR/Cognate Ligand Containing Genotypes Differ in Frequency Among Patients With Myeloma and Have an Effect on Age of Disease Onset

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dc.authoridCengiz Seval, Guldane/0000-0001-9433-2054
dc.authoridBeksac, Meral/0000-0003-1797-8657
dc.authoridAkin, H. Yalim/0000-0002-2461-9479
dc.authorid, RIDVAN GOKSEL/0000-0002-3871-8603
dc.authoridDalva, Klara/0000-0001-6917-6870
dc.authorwosidCengiz Seval, Guldane/GXV-6155-2022
dc.authorwosidBeksac, Meral/D-6411-2013
dc.authorwosidAkin, H. Yalim/IAS-0693-2023
dc.contributor.authorBeksac, Meral
dc.contributor.authorAkin, Hasan Yalim
dc.contributor.authorSeval, Guldane Cengiz
dc.contributor.authorMesutoglu, Pinar Yurdakul
dc.contributor.authorAnliacik, Ridvan Goksel
dc.contributor.authorAnliacik, Ezgi
dc.contributor.authorGurman, Gunhan
dc.date.accessioned2024-05-19T14:38:54Z
dc.date.available2024-05-19T14:38:54Z
dc.date.issued2023
dc.departmentİstinye Üniversitesien_US
dc.description.abstractKIR and KIR-ligand frequencies, alone or in combination, among MM (n:204) and healthy subjects (n:424) showed cAB1 as a specificity delaying onset of MM in the presence of C1C2 and AA as a predisposing one in the presence of C1C1 to be associated with earlier onset. Findings independent of R-ISS suggesting an immune modulating role of KIR plus ligand genotypes. Background: Natural killer (NK) cells are known to have cytotoxic effects mediated through killer immunoglobulin-like receptors (KIRs) and their cognate ligands. Role of KIRs in myeloma is yet unresolved. Patients and Methods: KIR genotypes and ligands of 204 newly diagnosed MM patients are compared with 424 healthy subjects. Statistical analysis included t-test, chi-square and binary logistic regression. Results: KIR ligands were significantly more (C2C2: 27.5% vs 15.1%; OR 2.128; 95% CI, 1.417-3.196; P < .001) or less (C1C2: 40.2% vs 51.9%; OR 0.623; 95% CI, 0.444-0.874; P = .006) frequent among MM. Co-occurrence of genotype AA with C2C2 was also higher in frequency among MM (OR 2.509; 95% CI, 1.171-5.378; P = .015) likewise cAB1 with C1C2 was less frequent (OR 0.553; 95% CI, 0.333-0.919; P = .021). Genotypes AA with C1C1, cAB1 with C1C2 or C1C2 alone were associated with a delay (median age: 61 [48-73]; P = .044; 62 [31-81]; P = .030 or 59 [31-85]; P = .028), but AA with C2C2 with an earlier age of onset (48 [29-77]; P = .042). In multivariate analysis including R-ISS, light chain, KIR genotype/ligands; ligand C1C2 ( P = .02) and genotype AA-C1C1 ( P = .037) were independently associated with age of onset & GE;60. Conclusion: C1C2 and C2C2 alone or in combination with KIR genotype (cAB1 and AA, respectively), is observed in less or higher frequency among MM cases and associated with delayed/earlier age of onset, respectively. Genotype AA-C1C1 although in similar frequency between patients and healthy subjects, is also associated with delay. To our knowledge, this is the first study demonstrating an association between KIR and MM onset age, independent from R-ISS or light chain type.en_US
dc.description.sponsorshipTUBITAK 3501 research grant [115S579]; Turkish Academy of Sciences research granten_US
dc.description.sponsorshipThis study was supported by TUBITAK 3501 research grant (115S579) and Turkish Academy of Sciences research grant.en_US
dc.identifier.doi10.1016/j.clml.2023.02.007
dc.identifier.issn2152-2650
dc.identifier.issn2152-2669
dc.identifier.issue5en_US
dc.identifier.pmid36918304en_US
dc.identifier.scopus2-s2.0-85151949729en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.urihttps://doi.org10.1016/j.clml.2023.02.007
dc.identifier.urihttps://hdl.handle.net/20.500.12713/4646
dc.identifier.volume23en_US
dc.identifier.wosWOS:001042771500001en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherCig Media Group, Lpen_US
dc.relation.ispartofClinical Lymphoma Myeloma & Leukemiaen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.snmz20240519_kaen_US
dc.subjectAge Of Onseten_US
dc.subjectInnate Immunityen_US
dc.subjectMultiple Myelomaen_US
dc.subjectNatural Killer Cellen_US
dc.subjectKiller Immunoglobulin-Like Receptors (Kir)en_US
dc.titleA Novel Hypothesis: Certain KIR/Cognate Ligand Containing Genotypes Differ in Frequency Among Patients With Myeloma and Have an Effect on Age of Disease Onseten_US
dc.typeArticleen_US

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