Emergence of clonal hematopoiesis in the majority of patients with acquired aplastic anemia

Publication date: Available online 2 February 2015 Source:Cancer Genetics Author(s): Daria V. Babushok , Nieves Perdigones , Juan C. Perin , Timothy S. Olson , Wenda Ye , Jacquelyn J. Roth , Curt Lind , Carine Cattier , Yimei Li , Helge Hartung , Michele E. Paessler , Dale M. Frank , Hongbo M. Xie , Shanna Cross , Joshua D. Cockroft , Gregory M. Podsakoff , Dimitrios Monos , Jaclyn A. Biegel , Philip J. Mason , Monica Bessler Acquired aplastic anemia (aAA) is a nonmalignant disease caused by autoimmune destruction of early hematopoietic cells. Clonal hematopoiesis is a late complication, seen in 20–25% of older patients. We hypothesized that clonal hematopoiesis in aAA is a more general phenomenon, which can arise early in disease, even in younger patients. To evaluate clonal hematopoiesis in aAA, we used comparative whole exome sequencing of paired bone marrow and skin samples in 22 patients. We found somatic mutations in 16 patients (72.7%) with a median disease duration of 1 year; of these, 12 (66.7%) were patients with pediatric-onset aAA. Fifty-eight mutations in 51 unique genes were found primarily in pathways of immunity and transcriptional regulation. Most frequently mutated was PIGA, with seven mutations. Only two mutations were in genes recurrently mutated in myelodysplastic syndrome. Two patients had oligoclonal loss of the HLA alleles, linking immune escape to clone emergence. Two patients had activating mutations in key signaling pathwa...
Source: Cancer Genetics - Category: Cancer & Oncology Source Type: research