Scientists uncover how cells survive in a rare childhood blood disorder

Scientists from St. Jude Children’s Research Hospital, together with international partners, have presented the largest study to date on aplastic anemia.

The work, published in Nature Genetics, is based on the analysis of 619 patients—both children and adults—using advanced genomic technologies, including single-cell sequencing.

Aplastic anemia is a rare and potentially life-threatening blood disorder in which the immune system mistakenly attacks hematopoietic stem cells in the bone marrow.

As a result, the body loses its ability to produce enough blood cells, which can lead to severe complications, including progression to myelodysplastic syndrome or leukemia.

The study’s main finding explains how some cells still manage to survive. Researchers discovered that different stem cells within the same patient independently acquire genetic changes that allow them to evade immune system attacks. These cells effectively become “invisible” to the autoimmune response and continue producing blood.

A key role is played by the HLA system—a group of genes responsible for how the immune system recognizes cells. Typically, a person inherits two variants of HLA, and certain combinations are associated with a higher risk of disease. Some stem cells develop changes that disable the “risky” HLA variant or replace it with a safer one.

In addition, other escape mechanisms were identified, including changes characteristic of paroxysmal nocturnal hemoglobinuria, as well as mutations in genes linked to clonal hematopoiesis (CHIP). For a long time, it was unclear whether these changes occurred sequentially in the same cell or independently in different ones.

The new data show that these are, in fact, multiple independent events. A single patient may develop several distinct “rescue” clones of stem cells that are not related to each other. On average, about three such clones are observed, and in some cases up to fifteen.

These clones gradually repopulate the bone marrow, restoring blood formation. In some patients, this leads to long-term remission. Importantly, researchers found no link between these “rescued” cells and an increased risk of leukemia—on the contrary, they may be associated with a more favorable prognosis.

Interestingly, the frequency of such mutations was found to be similar in children and adults, although the genes involved differ somewhat. Moreover, some clones appear long before diagnosis—sometimes years before symptoms develop.

The scientists also noted that surviving clones are often characterized by increased expression of the CD34 marker, which could potentially be used as a biomarker for the recovery of blood formation.

Overall, the study shows that aplastic anemia is not only a destructive autoimmune process but also a system in which the body can carry out an internal “selection” of cells resistant to immune attack. The authors describe this as a form of convergent evolution within the human bone marrow, where different cells independently arrive at the same solution—a way to survive.

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