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. 2014 Dec 1;20(23):5986-94.
doi: 10.1158/1078-0432.CCR-14-0479. Epub 2014 Oct 3.

NK cell genotype and phenotype at diagnosis of acute lymphoblastic leukemia correlate with postinduction residual disease

Erin M Sullivan  1 , Sima Jeha  2 , Guolian Kang  3 , Cheng Cheng  3 , Barbara Rooney  1 , Martha Holladay  1 , Rafijul Bari  1 , Sarah Schell  1 , MaCal Tuggle  1 , Ching-Hon Pui  2 , Wing Leung  4
Affiliations

NK cell genotype and phenotype at diagnosis of acute lymphoblastic leukemia correlate with postinduction residual disease

Erin M Sullivan et al. Clin Cancer Res. .

Abstract

Purpose: Not all natural killer (NK) cells are equally cytotoxic against leukemia because of differences in receptor gene content and surface expression. We correlated NK cell genotype and phenotype at diagnosis of childhood acute lymphoblastic leukemia (ALL) with minimal residual disease (MRD) after induction chemotherapy.

Experimental design: The NK cells and leukemia blasts of 244 patients were analyzed at diagnosis by killer-cell immunoglobulin-like receptor (KIR) typing and immunophenotyping. The results were correlated statistically with postinduction MRD status.

Results: The odds of being MRD positive in patients with KIR telomeric (Tel)-A/B genotype were 2.85 times the odds in those with Tel-A/A genotype (P = 0.035). MRD-positive patients were more likely to have KIR2DL5A (P = 0.006) and expressed less activating receptor NKp46 and FASL on their NK cells (P = 0.0074 and P = 0.029, respectively). The odds of being MRD positive increased by 2.01-fold for every percentage increase in NK cells expressing KIR2DL1 in the presence of HLA-C2 ligand (P = 0.034). The quantity of granzyme B inhibitor PI-9 in the leukemia blasts was greater in patients who were MRD positive (P = 0.038). Collectively, five NK cell-related factors (Tel-B-associated KIR2DL5A, NKp46, FASL, granzyme B, and PI-9) are strongly associated with MRD positivity at the end of induction with 100% sensitivity and 80% specificity.

Conclusions: Our data support the hypothesis that NK cells with a strong effector phenotype in the setting of decreased leukemia resistance are associated with better leukemia control.

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Conflict of interest statement

Conflicts of Interest Disclosures:

Erin Sullivan, Sima Jeha, Guolian Kang, Barbara Rooney, Martha Holladay, Rafijul Bari, Sarah Schell, MaCal Tuggle, and Wing Leung have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Simplified maps of the A and B KIR haplotypes on chromosome 19q13.4. Cen-B is KIR2DL2 positive and KIR2DL3 negative in the centromeric motifs and Tel-B is KIR3DS1 positive and KIR3DL1 negative in the telomeric motifs.
Figure 2
Figure 2
The five NK cell related factors were analyzed either singly or as composite in correlation with post-induction MRD. The composite model has a 100% sensitivity (or 100% true positivity) and an 80% specificity (or 20% false positivity).
See this image and copyright information in PMC

References

    1. Imai K, Matsuyama S, Miyake S, Suga K, Nakachi K. Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population. Lancet. 2000;356:1795–9. - PubMed
    1. Caligiuri MA. Human natural killer cells. Blood. 2008;112:461–9. - PMC - PubMed
    1. Costello RT, Sivori S, Marcenaro E, Lafage-Pochitaloff M, Mozziconacci MJ, Reviron D, et al. Defective expression and function of natural killer cell-triggering receptors in patients with acute myeloid leukemia. Blood. 2002;99:3661–7. - PubMed
    1. Fauriat C, Just-Landi S, Mallet F, Arnoulet C, Sainty D, Olive D, et al. Deficient expression of NCR in NK cells from acute myeloid leukemia: Evolution during leukemia treatment and impact of leukemia cells in NCRdull phenotype induction. Blood. 2007;109:323–30. - PubMed
    1. Nasrallah AG, Miale TD. Decreased natural killer cell activity in children with untreated acute leukemia. Cancer Res. 1983;43:5580–5. - PubMed

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