Homozygosity for killer immunoglobin-like receptor haplotype A predicts complete molecular response to treatment with tyrosine kinase inhibitors in chronic myeloid leukemia patients
| Autor: | N Orru, Marianna Greco, Andrea Floris, Sandro Orru, Marzia Langiu, S Atzeni, Carlo Carcassi, Adriana Vacca, Giovanni Caocci, Roberto Littera, Giorgio La Nasa, Olga Mulas |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Cancer Research Time Factors Genotype Kaplan-Meier Estimate Biology Young Adult Gene Frequency Receptors KIR Leukemia Myelogenous Chronic BCR-ABL Positive Genetics Humans Cumulative incidence Receptor Protein Kinase Inhibitors Molecular Biology Gene Aged Aged 80 and over Remission Induction Haplotype Myeloid leukemia Cell Biology Hematology Middle Aged Prognosis Logistic Models Treatment Outcome Haplotypes Receptors KIR2DL2 Immunology biology.protein Female Complete Molecular Response Antibody Tyrosine kinase Follow-Up Studies |
| Zdroj: | Experimental Hematology. 41:424-431 |
| ISSN: | 0301-472X |
| Popis: | Several recent reports suggest a possible role for killer immunoglobulin-like receptors (KIR) in the onset of chronic myeloid leukemia (CML) and response to therapy with tyrosine kinase inhibitors (TKIs). To explore this hypothesis, we studied KIRs and their human leukocyte antigen class I ligands in 59 consecutive patients with chronic-phase CML (mean age, 53 years; range, 23–81 years) and a group of 121 healthy control participants belonging to the same ethnic group as the patients. The 2-year cumulative incidence of complete molecular response, obtained after a median of 27 months (range, 4–52 months), was 51.2%. An increased frequency of the activating receptor KIR2DS1 ( pm = 0.05) and a reduced frequency of the KIR-ligand combination KIR2DS2/2DL2 absent/C1 present ( pm = 0.001) were significantly associated with CML. Moreover, KIR repertoires in patients appeared to influence response to TKI therapy. Homozygosity for KIR haplotype A ( pm = 0.01), a decreased frequency of the inhibitory KIR gene KIR2DL2 ( pm = 0.02), and low numbers of inhibitory KIR genes ( pm = 0.05) were all significantly associated with achievement of complete molecular remission. These data suggest that a decrease in properly stimulated and activated NK cells might contribute to the occurrence of CML and indicate homozygosity for KIR haplotype A as a promising immunogenetic marker of complete molecular response that could help clinicians decide whether to withdraw treatment in patients with CML. |
| Databáze: | OpenAIRE |
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