Clonal evolution in aplastic anemia: failed tumor surveillance or maladaptive recovery?

Abstract

Clonal evolution to secondary paroxysmal nocturnal hemoglobinuria (PNH) or myeloid neoplasia (MN) represents one of the long-term complications of patients with aplastic anemia (AA). The recent evidence in the field of immunology and the application of next-generation sequencing have shed light on the molecular underpinnings of these clonal complications, revealing clinical and molecular risk factors as well as potential immunological players. Particularly, whether MN evolution represents a failed tumor surveillance or a maladaptive recovery is still a matter of controversy in the field of bone marrow failure syndromes. However, recent studies have explored the precise dynamics of the immune-molecular forces governing such processes over time, generating knowledge useful for potential early therapeutic strategies. In this review, we will discuss the immune pathophysiology of AA and the emergence of clonal hematopoiesis with regard to the adaptive and maladaptive mechanisms at the basis of secondary evolution trajectories operating under the immune pressure.

Keywords:

• Aplastic anemia
• clonal evolution
• genomic profiling
• immune escape
• human leukocyte antigen (HLA
• )
• paroxysmal nocturnal hemoglobinuria (PNH)

Author contributions

C.G., S.P. and J.P.M. wrote the manuscript. All authors read and approved the final version of the manuscript and are accountable for all aspects of the work.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.