Clonal evolution and clinical significance of copy number neutral loss of heterozygosity of chromosome arm 6p in acquired aplastic anemia.

Abstract	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.
Authors	Marisol Betensky, Daria Babushok, Jacquelyn J Roth, Philip J Mason, Jaclyn A Biegel, Tracy M Busse, Yimei Li, Curt Lind, Anna Papazoglou, Dimitri Monos, Gregory Podsakoff, Monica Bessler, Timothy S Olson
Journal	Cancer genetics (Cancer Genet) 2016 Jan-Feb Vol. 209 Issue 1-2 Pg. 1-10 ISSN: 2210-7762 [Print] United States
PMID	26702937 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Copyright	Copyright © 2016 Elsevier Inc. All rights reserved.
Topics	Adolescent Adult Aged Anemia, Aplastic (genetics) Child Child, Preschool Chromosomes, Human, Pair 6 Clonal Evolution DNA Copy Number Variations Female Humans Infant Infant, Newborn Loss of Heterozygosity Male Middle Aged Polymorphism, Single Nucleotide Young Adult

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