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KIR2DS1 genotype predicts for complete cytogenetic response and survival in newly diagnosed chronic myeloid leukemia patients treated with imatinib

Lookup NU author(s): Professor Stephen O'Brien, Corinne Hedgley


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Natural killer (NK) cells are expanded in chronic myeloid leukemia (CML) patients on tyrosine kinase inhibitors (TKI) and exert cytotoxicity. The inherited repertoire of killer immunoglobulin-like receptors (KIR) may influence response to TKI. We investigated the impact of KIR-genotype on outcome in 166 chronic phase CML patients on first-line imatinib treatment. We validated our findings in an independent patient group. On multivariate analysis, KIR2DS1 genotype (RR=1.51, P=0.03) and Sokal risk score (low-risk RR=1, intermediate-risk RR=1.53, P=0.04, high-risk RR=1.69, P=0.034) were the only independent predictors for failure to achieve complete cytogenetic response (CCyR). Furthermore, KIR2DS1 was the only factor predicting shorter progression-free (PFS) (RR=3.1, P=0.03) and overall survival (OS) (RR=2.6, P=0.04). The association between KIR2DS1 and CCyR, PFS and OS was validated by KIR genotyping in 174 CML patients on first-line imatinib in the UK multi-center SPIRIT-1 trial; in this cohort, KIR2DS1(+) patients had significantly lower 2-year probabilities of achieving CCyR (76.9 vs 87.9%, P=0.003), PFS (85.3 vs 98.1%, P=0.007) and OS (94.4 vs 100%, P=0.015) than KIR2DS1(-) patients. The impact of KIR2DS1 on CCyR was greatest when the ligand for the corresponding inhibitory receptor, KIR2DL1, was absent (P=0.00006). Our data suggest a novel role for KIR-HLA immunogenetics in CML patients on TKI. Leukemia (2012) 26, 296-302; doi:10.1038/leu.2011.180; published online 16 August 2011

Publication metadata

Author(s): Marin D, Gabriel IH, Ahmad S, Foroni L, de Lavallade H, Clark R, O'Brien S, Sergeant R, Hedgley C, Milojkovic D, Khorashad JS, Bua M, Alsuliman A, Khoder A, Stringaris K, Cooper N, Davis J, Goldman JM, Apperley JF, Rezvani K

Publication type: Article

Publication status: Published

Journal: Leukemia

Year: 2012

Volume: 26

Issue: 2

Pages: 296-302

Print publication date: 16/08/2011

ISSN (print): 0887-6924

ISSN (electronic): 1476-5551

Publisher: Nature Publishing Group


DOI: 10.1038/leu.2011.180


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Funder referenceFunder name
National Institute for Health Research (NIHR) Biomedical Research Center (BRC), United Kingdom
NCRN CML working group, United Kingdom
286231Leuka registered charity
P31514NIHR BRC London