TY - JOUR
T1 - Following transplantation for acute myelogenous leukemia, donor KIR cen B02 better protects against relapse than KIR Cen B01
AU - Guethlein, Lisbeth A.
AU - Beyzaie, Niassan
AU - Nemat-Gorgani, Neda
AU - Wang, Tao
AU - Ramesh, Vidhyalakshmi
AU - Marin, Wesley M.
AU - Hollenbach, Jill A.
AU - Schetelig, Johannes
AU - Spellman, Stephen R
AU - Marsh, Steven G.E.
AU - Cooley, Sarah A
AU - Weisdorf, Daniel J
AU - Norman, Paul J.
AU - Miller, Jeffrey S.
AU - Parham, Peter
N1 - Funding Information:
This work was supported by National Institutes of Health, National Cancer Institute Grant P01 CA111412 to J.M.
Publisher Copyright:
Copyright © 2021 by The American Association of Immunologists, Inc.
PY - 2021/6/15
Y1 - 2021/6/15
N2 - In the treatment of acute myelogenous leukemia with allogeneic hematopoietic cell transplantation, we previously demonstrated that there is a greater protection from relapse of leukemia when the hematopoietic cell transplantation donor has either the Cen B/B KIR genotype or a genotype having two or more KIR B gene segments. In those earlier analyses, KIR genotyping could only be assessed at the low resolution of gene presence or absence. To give the analysis greater depth, we developed high-resolution KIR sequence-based typing that defines all the KIR alleles and distinguishes the expressed alleles from those that are not expressed. We now describe and analyze high-resolution KIR genotypes for 890 donors of this human transplant cohort. Cen B01 and Cen B02 are the common CenB haplotypes, with Cen B02 having evolved from Cen B01 by deletion of the KIR2DL5, 2DS3/5, 2DP1, and 2DL1 genes. We observed a consistent trend for Cen B02 to provide stronger protection against relapse than Cen B01. This correlation indicates that protection depends on the donor having inhibitory KIR2DL2 and/or activating KIR2DS2, and is enhanced by the donor lacking inhibitory KIR2DL1, 2DL3, and 3DL1. High-resolution KIR typing has allowed us to compare the strength of the interactions between the recipient's HLA class I and the KIR expressed by the donor-derived NK cells and T cells, but no clinically significant interactions were observed. The trend observed between donor Cen B02 and reduced relapse of leukemia points to the value of studying ever larger transplant cohorts.
AB - In the treatment of acute myelogenous leukemia with allogeneic hematopoietic cell transplantation, we previously demonstrated that there is a greater protection from relapse of leukemia when the hematopoietic cell transplantation donor has either the Cen B/B KIR genotype or a genotype having two or more KIR B gene segments. In those earlier analyses, KIR genotyping could only be assessed at the low resolution of gene presence or absence. To give the analysis greater depth, we developed high-resolution KIR sequence-based typing that defines all the KIR alleles and distinguishes the expressed alleles from those that are not expressed. We now describe and analyze high-resolution KIR genotypes for 890 donors of this human transplant cohort. Cen B01 and Cen B02 are the common CenB haplotypes, with Cen B02 having evolved from Cen B01 by deletion of the KIR2DL5, 2DS3/5, 2DP1, and 2DL1 genes. We observed a consistent trend for Cen B02 to provide stronger protection against relapse than Cen B01. This correlation indicates that protection depends on the donor having inhibitory KIR2DL2 and/or activating KIR2DS2, and is enhanced by the donor lacking inhibitory KIR2DL1, 2DL3, and 3DL1. High-resolution KIR typing has allowed us to compare the strength of the interactions between the recipient's HLA class I and the KIR expressed by the donor-derived NK cells and T cells, but no clinically significant interactions were observed. The trend observed between donor Cen B02 and reduced relapse of leukemia points to the value of studying ever larger transplant cohorts.
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U2 - 10.4049/jimmunol.2100119
DO - 10.4049/jimmunol.2100119
M3 - Article
C2 - 34117109
AN - SCOPUS:85108637672
SN - 0022-1767
VL - 206
SP - 3064
EP - 3072
JO - Journal of Immunology
JF - Journal of Immunology
IS - 12
ER -