Comprehensive analysis of the clinical feature, myeloid neoplasm-related gene mutation profiles and T cell diversity acquired pure red cell aplasia

TL;DR

This study analyzes clinical features, gene mutations, and T cell diversity in pure red cell aplasia to better understand its causes and treatment responses.

Contribution

The study provides a comprehensive analysis of gene mutations and TCR profiles in a large PRCA cohort, identifying key factors associated with treatment response.

Findings

DNMT3A, KMT2A, and TP53 are the top mutated genes in acquired PRCA patients over 40 years old.

TRBV6_TRBJ2 is the most frequent dominant clonotype in LGLL-associated PRCA patients.

CsA response in PRCA is influenced by β2-MG and MF dysregulation, not by gene mutations or TCR clone numbers.

Abstract

Acquired pure red cell aplasia (PRCA) is a kind of rare bone marrow failure disease characterized by destruction of erythrocyte by the immune system. However, the diverse etiologies of acquired PRCA make its pathogenesis largely unclear.

We portrayed the clinicopathologic, mutation and TCR rearrangement profiles of 64 primary PRCA cases and 104 large granular lymphocytic leukemia (LGLL)-associated PRCA, and tried to reveal the association factors of CsA response.

We found that gene mutations were detected in 39.7% of acquired PRCA who were older than 40 years, with DNMT3A, KMT2A and TP53 being the top 3 mutation genes. KMT2A mutation was only detected in patients with normal reticulocyte (Ret)%, while IDH1 mutation only occurred in patients with normal CD3 + CD8+/Lym%. For LGLL-associated PRCA patients, TRBV6_TRBJ2 was the most frequent dominant clonotype and the proportion of each dominant clone decreased following the remission of anemia. The response rate of LGLL-associated PRCA to CsA treatment was lower than primary PRCA (56.4% vs. 77.4%). β2-MG dysregulation, MF dysregulation were unfavorable factors for the response to CsA in PRCA patients, while other clinical information, mutated genes, number of mutated genes, mean VAF, number of TCR clones in PRCA patients did not significantly affect the response to CsA.

This study described the clinical features, mutation landscape and TCR rearrangement profile in a relatively larger PRCA cohort, which may contribute to the clear perception of PRCA and the development of more potent treatment approaches.

The online version contains supplementary material available at 10.1007/s00277-025-06638-x.

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