title: Homozygosity for killer immunoglobin-like receptor haplotype A predicts complete molecular response to treatment with tyrosine kinase inhibitors in chronic myeloid leukemia patients.
abstract: 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.
authors: Bone Marrow Transplant Center, R. Binaghi Hospital - ASL 8, Cagliari, Italy. lanasa@tiscali.it
authors: Giorgio
authors: G
authors: La Nasa
authors: Giovanni
authors: G
authors: Caocci
authors: Roberto
authors: R
authors: Littera
authors: Sandra
authors: S
authors: Atzeni
authors: Adriana
authors: A
authors: Vacca
authors: Olga
authors: O
authors: Mulas
authors: Marzia
authors: M
authors: Langiu
authors: Marianna
authors: M
authors: Greco
authors: Sandro
authors: S
authors: Orrù
authors: Nicola
authors: N
authors: Orrù
authors: Andrea
authors: A
authors: Floris
authors: Carlo
authors: C
authors: Carcassi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D053208:Kaplan-Meier Estimate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D054340:Receptors, KIR / Q000235:genetics*; D054343:Receptors, KIR2DL2 / Q000235:genetics; D012074:Remission Induction; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C515077:KIR2DL2 protein, human; C496212:KIR2DS1 protein, human; C433932:KIR2DS2 protein, human; D047428:Protein Kinase Inhibitors; D054340:Receptors, KIR; D054343:Receptors, KIR2DL2