Clonal hematopoiesis in adult pure red cell aplasia

Abstract

Idiopathic pure red cell aplasia (PRCA) and secondary PRCA associated with thymoma and large granular lymphocyte leukemia are generally considered to be immune-mediated. The PRCA2004/2006 study showed that poor responses to immunosuppression and anemia relapse were associated with death. PRCA may represent the prodrome to MDS. Thus, clonal hematopoiesis may be responsible for treatment failure. We investigated gene mutations in myeloid neoplasm-associated genes in acquired PRCA. We identified 21 mutations affecting amino acid sequences in 11 of the 38 adult PRCA patients (28.9%) using stringent filtering of the error-prone sequences and SNPs. Four PRCA patients showed 7 driver mutations in TET2, DNMT3A and KDM6A, and 2 PRCA patients carried multiple mutations in TET2. Five PRCA patients had mutations with high VAFs exceeding 0.3. These results suggest that clonal hematopoiesis by stem/progenitor cells might be related to the pathophysiology of chronic PRCA in certain adult patients.

Figure 1

Landscape of gene mutation in PRCA. Overall genomic alterations are shown here. Each row indicates a distinct genomic alteration, and each column shows the results of the respective individual. Upper and lower panels show mutations in coding and noncoding regions, respectively. Mutations with high VAFs (> 0.40) and low VAFs (≤ 0.40) are depicted in red and blue, respectively. None of the 13 healthy control donors showed any genomic alterations.