PMID- 20124217 OWN - NLM STAT- MEDLINE DCOM- 20100430 LR - 20210206 IS - 1528-0020 (Electronic) IS - 0006-4971 (Linking) VI - 115 IP - 15 DP - 2010 Apr 15 TI - Relapse of leukemia with loss of mismatched HLA resulting from uniparental disomy after haploidentical hematopoietic stem cell transplantation. PG - 3158-61 LID - 10.1182/blood-2009-11-254284 [doi] AB - 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. FAU - Villalobos, Itzel Bustos AU - Villalobos IB AD - Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan. FAU - Takahashi, Yoshiyuki AU - Takahashi Y FAU - Akatsuka, Yoshiki AU - Akatsuka Y FAU - Muramatsu, Hideki AU - Muramatsu H FAU - Nishio, Nobuhiro AU - Nishio N FAU - Hama, Asahito AU - Hama A FAU - Yagasaki, Hiroshi AU - Yagasaki H FAU - Saji, Hiroh AU - Saji H FAU - Kato, Motohiro AU - Kato M FAU - Ogawa, Seishi AU - Ogawa S FAU - Kojima, Seiji AU - Kojima S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100201 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (HLA Antigens) RN - 0 (Isoantigens) SB - IM MH - Blast Crisis/genetics/immunology MH - Child MH - Chromosomes, Human, Pair 6/genetics MH - Cytotoxicity, Immunologic MH - HLA Antigens/*immunology MH - *Haploidy MH - *Hematopoietic Stem Cell Transplantation MH - *Histocompatibility Testing MH - Humans MH - Isoantigens/immunology MH - Leukemia/*immunology MH - Recurrence MH - T-Lymphocytes, Cytotoxic/immunology MH - Tissue Donors MH - Uniparental Disomy/*genetics EDAT- 2010/02/04 06:00 MHDA- 2010/05/01 06:00 CRDT- 2010/02/04 06:00 PHST- 2010/02/04 06:00 [entrez] PHST- 2010/02/04 06:00 [pubmed] PHST- 2010/05/01 06:00 [medline] AID - S0006-4971(20)56504-X [pii] AID - 10.1182/blood-2009-11-254284 [doi] PST - ppublish SO - Blood. 2010 Apr 15;115(15):3158-61. doi: 10.1182/blood-2009-11-254284. Epub 2010 Feb 1.