PMID- 29695383
OWN - NLM
STAT- MEDLINE
DCOM- 20190425
LR  - 20190425
IS  - 2326-6074 (Electronic)
IS  - 2326-6066 (Linking)
VI  - 6
IP  - 6
DP  - 2018 Jun
TI  - Allelic Polymorphisms of KIRs and HLAs Predict Favorable Responses to Tyrosine 
      Kinase Inhibitors in CML.
PG  - 745-754
LID - 10.1158/2326-6066.CIR-17-0462 [doi]
AB  - Response to tyrosine kinase inhibitors (TKIs) is variable in chronic myeloid 
      leukemia (CML), and elevated natural killer (NK) cells during TKI therapy are 
      positively correlated with superior outcomes. NK cell function involves 
      interactions of their killer immunoglobulin-like receptors (KIRs) and human 
      leukocyte antigen (HLA) class I on target cells, and the avidity of KIR-HLA 
      interactions depends on the combination of KIR and HLA alleles. We hypothesized 
      that KIR and HLA polymorphisms may influence response to TKIs. KIR and HLA allele 
      genotyping was performed by next-generation sequencing for 76 CML cases, and 
      association with clinical outcome was analyzed. Second-generation TKIs as 
      first-line therapy and patients' sex (female) were strongly associated with 
      achievement of complete molecular response (CMR: MR(4.0)) after 2 years (P < 
      0.001 and P = 0.002, respectively). After adjustment for these two 
      characteristics, several KIR alleles remained associated with achievement of 
      MR(4.0): KIR2DL4*005/011 or *008 (HR = 1.797, P = 0.032); KIR2DS4*003 or *007/010 
      (HR = 3.348, P < 0.001); KIR3DL1*005 (HR = 2.746, P = 0.003); and KIR3DL2*009 or 
      *010 [HR = 1.980 (1.109-3.524), P = 0.021]. Strong linkage among these alleles 
      exists, implying that they comprise favorable KIR allele haplotypes. Allelic 
      polymorphisms of KIR3DL1 and HLA-B determine their differential avidity into 
      strong/weak or no interaction. Patients carrying noninteracting KIR3DL1 and HLA-B 
      allele pairs achieved better outcomes than those with strongly interacting pairs, 
      and KIR3DL1*005 associated with a positive outcome among patients with 
      weak-interacting pairs. Thus, KIR3DL1*005 and its associated haplotypes 
      associated with superior TKI therapeutic effects. The combinations of these KIR 
      and HLA alleles may correlate with potent NK cell immunity against CML. Cancer 
      Immunol Res; 6(6); 745-54. (c)2018 AACR.
CI  - (c)2018 American Association for Cancer Research.
FAU - Ureshino, Hiroshi
AU  - Ureshino H
AUID- ORCID: 0000-0002-5034-3699
AD  - Division of Hematology, Respiratory Medicine and Oncology, Department of Internal 
      Medicine, Faculty of Medicine, Saga University, Saga, Japan.
FAU - Shindo, Takero
AU  - Shindo T
AD  - Division of Hematology, Respiratory Medicine and Oncology, Department of Internal 
      Medicine, Faculty of Medicine, Saga University, Saga, Japan. 
      takeros@kuhp.kyoto-u.ac.jp.
AD  - Department of Hematology/Oncology, Kyoto University Graduate School of Medicine, 
      Kyoto, Japan.
FAU - Kojima, Hiroto
AU  - Kojima H
AD  - HLA Foundation Laboratory, Kyoto, Japan.
FAU - Kusunoki, Yasushi
AU  - Kusunoki Y
AD  - HLA Foundation Laboratory, Kyoto, Japan.
FAU - Miyazaki, Yuki
AU  - Miyazaki Y
AD  - HLA Foundation Laboratory, Kyoto, Japan.
FAU - Tanaka, Hidenori
AU  - Tanaka H
AD  - HLA Foundation Laboratory, Kyoto, Japan.
FAU - Saji, Hiroh
AU  - Saji H
AD  - HLA Foundation Laboratory, Kyoto, Japan.
FAU - Kawaguchi, Atsushi
AU  - Kawaguchi A
AD  - Center for Comprehensive Community Medicine, Faculty of Medicine, Saga 
      University, Saga, Japan.
FAU - Kimura, Shinya
AU  - Kimura S
AD  - Division of Hematology, Respiratory Medicine and Oncology, Department of Internal 
      Medicine, Faculty of Medicine, Saga University, Saga, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180425
PL  - United States
TA  - Cancer Immunol Res
JT  - Cancer immunology research
JID - 101614637
RN  - 0 (Biomarkers)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (HLA Antigens)
RN  - 0 (Receptors, KIR)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - *Alleles
MH  - Biomarkers
MH  - Biomarkers, Tumor
MH  - Female
MH  - HLA Antigens/*genetics/immunology
MH  - Haplotypes
MH  - Humans
MH  - Immunophenotyping
MH  - Killer Cells, Natural/immunology/metabolism
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug 
      therapy/*genetics/immunology/*mortality
MH  - Male
MH  - Middle Aged
MH  - *Pharmacogenomic Variants
MH  - *Polymorphism, Genetic
MH  - Prognosis
MH  - Protein-Tyrosine Kinases/pharmacology/therapeutic use
MH  - Receptors, KIR/*genetics
MH  - Treatment Outcome
MH  - Young Adult
EDAT- 2018/04/27 06:00
MHDA- 2019/04/26 06:00
CRDT- 2018/04/27 06:00
PHST- 2017/08/27 00:00 [received]
PHST- 2018/01/27 00:00 [revised]
PHST- 2018/04/20 00:00 [accepted]
PHST- 2018/04/27 06:00 [pubmed]
PHST- 2019/04/26 06:00 [medline]
PHST- 2018/04/27 06:00 [entrez]
AID - 2326-6066.CIR-17-0462 [pii]
AID - 10.1158/2326-6066.CIR-17-0462 [doi]
PST - ppublish
SO  - Cancer Immunol Res. 2018 Jun;6(6):745-754. doi: 10.1158/2326-6066.CIR-17-0462. 
      Epub 2018 Apr 25.