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

Research output: Contribution to journalArticle

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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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Uniparental Disomy
Hematopoietic Stem Cell Transplantation
HLA Antigens
Stem cells
Leukemia
Recurrence
Alleles
Immunologic Monitoring
Chromosomes, Human, Pair 6
Lymphocytes
Flow cytometry
Loss of Heterozygosity
Chromosomes
Polymorphism
Haplotypes
Single Nucleotide Polymorphism
Flow Cytometry
Nucleotides
Tissue Donors

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., ... 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
Villalobos, Itzel Bustos ; Takahashi, Yoshiyuki ; Akatsuka, Yoshiki ; Muramatsu, Hideki ; Nishio, Nobuhiro ; Hama, Asahito ; Yagasaki, Hiroshi ; Saji, Hiroh ; Kato, Motohiro ; Ogawa, Seishi ; Kojima, Seiji. / Relapse of leukemia with loss of mismatched HLA resulting from uniparental disomy after haploidentical hematopoietic stem cell transplantation. In: Blood. 2010 ; Vol. 115, No. 15. pp. 3158-3161.
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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.",
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Villalobos, IB, 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, vol. 115, no. 15, pp. 3158-3161. https://doi.org/10.1182/blood-2009-11-254284

Relapse of leukemia with loss of mismatched HLA resulting from uniparental disomy after haploidentical hematopoietic stem cell transplantation. / Villalobos, Itzel Bustos; Takahashi, Yoshiyuki; Akatsuka, Yoshiki; Muramatsu, Hideki; Nishio, Nobuhiro; Hama, Asahito; Yagasaki, Hiroshi; Saji, Hiroh; Kato, Motohiro; Ogawa, Seishi; Kojima, Seiji.

In: Blood, Vol. 115, No. 15, 15.04.2010, p. 3158-3161.

Research output: Contribution to journalArticle

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T1 - Relapse of leukemia with loss of mismatched HLA resulting from uniparental disomy after haploidentical hematopoietic stem cell transplantation

AU - Villalobos, Itzel Bustos

AU - Takahashi, Yoshiyuki

AU - Akatsuka, Yoshiki

AU - Muramatsu, Hideki

AU - Nishio, Nobuhiro

AU - Hama, Asahito

AU - Yagasaki, Hiroshi

AU - Saji, Hiroh

AU - Kato, Motohiro

AU - Ogawa, Seishi

AU - Kojima, Seiji

PY - 2010/4/15

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N2 - 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.

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.

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