Interaction between KIR3DS1 and HLA-Bw4 predicts for progression-free survival after autologous stem cell transplantation in patients with multiple myeloma

Gabriel, Ian; Sergeant, Ruhena; Szydlo, Richard; Apperley, Jane F.; deLavallade, Hugues; Alsuliman, Abdullah; Khoder, Ahmad; Marín, David; Kanfer, Edward; Cooper, Nichola; Davis, J. G.; Macdonald, Donald; Bua, Marco; Foroni, Letizia; Giles, Chrissy; Milojković, Dragana; Rahemtulla, Amin; Rezvani, Katayoun

doi:10.1182/blood-2010-03-273706

Cited by 44 publications

(44 citation statements)

References 48 publications

(63 reference statements)

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“…[30][31][32][33] We recently reported on the relationship between KIR genotype and outcome in the setting of autologous SCT for myeloma. 34 Using a large homogeneous cohort of newly diagnosed patients with CML-CP treated with imatinib, we show here that patients carrying the activating KIR gene KIR2DS1 have a significantly lower probability of achieving CCyR, and lower 2-year probabilities of PFS and OS compared with those who are KIR2DS1 negative. On the other hand, absence of KIR2DS1 was associated with better response to imatinib.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2011

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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 ¼ 1.51, P ¼ 0.03) and Sokal risk score (low-risk RR ¼ 1, intermediaterisk RR ¼ 1.53, P ¼ 0.04, high-risk RR ¼ 1.69, P ¼ 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 ¼ 3.1, P ¼ 0.03) and overall survival (OS) (RR ¼ 2.6, P ¼ 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( þ ) patients had significantly lower 2-year probabilities of achieving CCyR (76.9 vs 87.9%, P ¼ 0.003), PFS (85.3 vs 98.1%, P ¼ 0.007) and OS (94.4 vs 100%, P ¼ 0.015) than KIR2DS1(À) patients. The impact of KIR2DS1 on CCyR was greatest when the ligand for the corresponding inhibitory receptor, KIR2DL1, was absent (P ¼ 0.00006). Our data suggest a novel role for KIR-HLA immunogenetics in CML patients on TKI.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2011

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“…Conflicting data from clinical studies on transplantation outcome regarding KIR-ligand mismatch [17][18][19] and KIR genotype [20 -22] seem to be generated through different transplantation setups [23,24]. Several groups have elucidated the role of different KIR-ligand interactions in NK cell (allo-) reactivity by investigating the cytotoxic function of single NK cell subsets that express no or single KIR receptors [12][13][14][25][26][27][28]. However, NK cells that arise in patients after bone marrow transplantation will express every possible receptor combination provided by the genotype.…”

Section: Introductionmentioning

confidence: 99%

Assessment of physiologic natural killer cell cytotoxicity in vitro

et al. 2011

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“…However, it has been shown that in patients with MM, interaction between KIR3DL1/S1 and HLABw4 can predict PFS after autologous SCT. 31 The present study investigates the influence of KIR/HLA-I interactions involved in NK cell licensing on the susceptibility to and the progression of PCDs. Additionally, explores whether the expression of KIR receptors in NK cells or that of their ligands in malignant PCs, could determine NK cell functionality and the outcome of the disease.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of KIR inhibitory ligands (HLA-I) determines that immunosurveillance of myeloma depends on diverse and strong NK cell licensing

Martínez‐Sánchez¹,

Periago

Legáz³

et al. 2015

OncoImmunology

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L3¡ (20% vs. 83%, p < 0.00001) as well as KIR3DL1 ¡ (23% vs. 82%, p < 0.00001) genotypes had a dramatic negative impact on the 3-y progression-free survival (PFS), particularly in patients with lowtumor burden. Remarkably, myeloma-PCs, compared to K562 and other hematological cancers, showed substantial over-expression of HLA-I ("increasing-self" instead of missing-self), including HLA-C, and mild expression of ligands for NKc activating receptors (aRec) CD112, CD155, ULBP-1 and MICA/B, which apparently renders myeloma-PCs susceptible to lysis mainly by licensed NKc. KIR2DL1patients (with no conventional iKIR2D/HLA-C licensing interactions) lyse K562 but barely lyse myelomaPCs (4% vs. 15%; p < 0.05, compared to controls). These results support a model where immunosurveillance of no-missing-self cancers, e.g., myeloma, mainly depends on NKc licensing.

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Interaction between KIR3DS1 and HLA-Bw4 predicts for progression-free survival after autologous stem cell transplantation in patients with multiple myeloma

Cited by 44 publications

References 48 publications

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

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

Assessment of physiologic natural killer cell cytotoxicity in vitro

Overexpression of KIR inhibitory ligands (HLA-I) determines that immunosurveillance of myeloma depends on diverse and strong NK cell licensing

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