[HTML][HTML] Escape hematopoiesis by HLA-B5401-lacking hematopoietic stem progenitor cells in men with acquired aplastic anemia

MI Elbadry, H Mizumaki, K Hosokawa… - …, 2019 - ncbi.nlm.nih.gov
MI Elbadry, H Mizumaki, K Hosokawa, JL Espinoza, N Nakagawa, K Chonabayashi…
Haematologica, 2019ncbi.nlm.nih.gov
Leukocytes that lack HLA class I alleles derived from hematopoietic stem and progenitor
cells (HSPC) that undergo copy number-neutral loss of heterozygosity of the short arm of
chromosome 6 (6pLOH) or HLA allelic mutations are often detected in patients with aplastic
anemia (AA). The presence of HLA class I allele-lacking leukocytes provides compelling
evidence that cytotoxic T-lymphocytes (CTL) are involved in the development of AA, 1-5 but
the precise mechanisms underlying HLA lack and clonal hematopoiesis by such HLA (–) …
Leukocytes that lack HLA class I alleles derived from hematopoietic stem and progenitor cells (HSPC) that undergo copy number-neutral loss of heterozygosity of the short arm of chromosome 6 (6pLOH) or HLA allelic mutations are often detected in patients with aplastic anemia (AA). The presence of HLA class I allele-lacking leukocytes provides compelling evidence that cytotoxic T-lymphocytes (CTL) are involved in the development of AA, 1-5 but the precise mechanisms underlying HLA lack and clonal hematopoiesis by such HLA (–) HSPC is unknown.
We recently showed that B* 54: 01 was one of three HLA alleles that were most likely to be possessed by 6pLOH+ patients [29%(5/17)] when only patients not carrying HLA-B* 40: 02 were analyzed. 5 To gain insight into the mechanism underlying clonal hematopoiesis by HLA-B5401-lacking HSPC, we studied the role of HLAB* 54: 01 in the pathogenesis of AA in a larger number of patients as well as HSPC derived from induced pluripotent stem cells (iPSC) that were generated from an AA patient whose monocytes lacked B5401. A total of 733 AA patients were enrolled in an observational study to determine the prevalence of HLA class I allele-lacking leukocytes by GeneChip 500 K arrays (Affymetrix, Japan) and droplet digital polymerase chain reaction using a QX200 AutoDG Droplet Digital PCR System (Bio-Rad, Hercules, CA, USA) or a next-generation sequencer (MiSeq; Illumina, San Diego, CA, USA) as previously described. 1, 5 Informed consent was obtained from the study participants for the genetic analyses and iPSC generation. The diagnosis and severity of AA were determined according to standard criteria. 6 The character-
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