Relapse of leukemia with loss of mismatched HLA resulting from uniparental disomy after haploidentical hematopoietic stem cell transplantation.
We investigated human leukocyte antigen (HLA) expression on leukemic cells derived from patients at diagnosis and relapse after hematopoietic stem cell transplantation (HSCT) using flow cytometry with locus-specific antibodies. Two of 3 patients who relapsed after HLA-haploidentical HSCT demonstrated loss of HLA alleles in leukemic cells at relapse; on the other hand, no loss of HLA alleles was seen in 6 patients who relapsed after HLA-identical HSCT. Single-nucleotide polymorphism array analyses of sorted leukemic cells further revealed the copy number-neutral loss of heterozygosity, namely, acquired uniparental disomy on the short arm of chromosome 6, resulting in the total loss of the mismatched HLA haplotype. These results suggest that the escape from immunosurveillance by the loss of mismatched HLA alleles may be a crucial mechanism of relapse after HLA-haploidentical HSCT. Accordingly, the status of mismatched HLA on relapsed leukemic cells should be checked before donor lymphocyte infusion.
Villalobos
Itzel Bustos
IB
Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
Takahashi
Yoshiyuki
Y
Akatsuka
Yoshiki
Y
Muramatsu
Hideki
H
Nishio
Nobuhiro
N
Hama
Asahito
A
Yagasaki
Hiroshi
H
Saji
Hiroh
H
Kato
Motohiro
M
Ogawa
Seishi
S
Kojima
Seiji
S
D001752:Blast Crisis / Q000235:genetics / Q000276:immunology; D002648:Child; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D003602:Cytotoxicity, Immunologic; D006680:HLA Antigens / Q000276:immunology*; D006238:Haploidy; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D007519:Isoantigens / Q000276:immunology; D007938:Leukemia / Q000276:immunology*; D012008:Recurrence; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014019:Tissue Donors; D024182:Uniparental Disomy / Q000235:genetics*
D006680:HLA Antigens; D007519:Isoantigens