Relapse of leukemia with loss of mismatched HLA resulting from uniparental disomy after haploidentical hematopoietic stem cell transplantation

Itzel Bustos Villalobos, Yoshiyuki Takahashi, Yoshiki Akatsuka, Hideki Muramatsu, Nobuhiro Nishio, Asahito Hama, Hiroshi Yagasaki, Hiroh Saji, Motohiro Kato, Seishi Ogawa, Seiji Kojima

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Abstract

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.

Original languageEnglish
Pages (from-to)3158-3161
Number of pages4
JournalBlood
Volume115
Issue number15
DOIs
Publication statusPublished - 15-04-2010

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Villalobos, I. B., Takahashi, Y., Akatsuka, Y., Muramatsu, H., Nishio, N., Hama, A., Yagasaki, H., Saji, H., Kato, M., Ogawa, S., & Kojima, S. (2010). Relapse of leukemia with loss of mismatched HLA resulting from uniparental disomy after haploidentical hematopoietic stem cell transplantation. Blood, 115(15), 3158-3161. https://doi.org/10.1182/blood-2009-11-254284