Acquired aplastic anemia (aAA) results from the T cell-mediated autoimmune destruction
of hematopoietic stem cells. Factors predicting response to immune suppression therapy
(IST) or development of myelodysplastic syndrome (MDS) are beginning to be elucidated.
Our recent data suggest most patients with aAA treated with IST develop clonal somatic
genetic alterations in hematopoietic cells. One frequent acquired abnormality is copy-number
neutral loss of heterozygosity on chromosome 6p (6p CN-LOH) involving the human leukocyte
antigen (HLA) locus. We hypothesized that because 6p CN-LOH clones may arise from
selective pressure to escape immune surveillance through deletion of HLA alleles,
the development of 6p CN-LOH may affect response to IST. We used single nucleotide
polymorphism array genotyping and targeted next-generation sequencing of HLA alleles
to assess frequency of 6p CN-LOH, identity of HLA alleles lost through 6p CN-LOH,
and impact of 6p CN-LOH on response to IST. 6p CN-LOH clones were present in 11.3%
of patients, remained stable over time, and were not associated with development of
MDS-defining cytogenetic abnormalities. Notably, no patient with 6p CN-LOH treated
with IST achieved a complete response. In summary, clonal 6p CN-LOH in aAA defines
a unique subgroup of patients that may provide insights into hematopoietic clonal
evolution.
Keywords
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Article Info
Publication History
Published online: October 30, 2015
Accepted:
October 19,
2015
Received:
October 16,
2015
Identification
Copyright
© 2016 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
