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Letters to the Editor
Figure 2. Models of clonal evolution in seven patients with donor cell myeloid neoplasm (DCMN) post-allogeneic stem cell transplantation (allo-HSCT). Figures of clonal evolution showed the dynamics of somatic mutations prob- ably related to the onset of donor cell leukemia after allo-HSCT.
toxicity in the BM of prior chemotherapy and/or TBI plays an important role in pathophysiology of this disease. Of note, none of the donors had received chemotherapeutic or other toxic drugs.
Additionally, the post allo-HSCT period is characterized by a decreased immune surveillance caused by both con- ditioning regimens and by the immunosuppressive drugs administered to prevent graft-versus-host disease. Downregulation or inactivation of the immune system may facilitate malignant clonal progression. Consequently, the appearance or outgrowth of cells with potential to become cancerous is increased in this period.
Noteworthy, all seven donors in the present study had germline or acquired genetic alterations in genes which might be related to tumor development. Although some of the specific variants found in the donors have been described in low frequencies in particular human popula-
tions, all of them have also been previously described in families with a predisposition to cancer. Cancer-related genes usually show incomplete penetrance and variable expressivity, and need additional genomic events to lead to the development of a tumor.11 In this regard, post-SCT conditions might contribute to the progression of the phe- notype. The existence of an acquired premalignant state bearing the initiating lesions has been reported in some donors who have no other signs of disease. Moreover, somatic mutations in genes involved in leukemogenesis were found in 5%, 10% and 20% of 60-, 70-, and 90-year- old individuals, respectively.12 Likewise, humans with clonal hematopoiesis have an increased risk of developing hematologic neoplasms compared with those without mutations.13 However, the use of older donors with clonal hematopoiesis of indeterminate potential (CHIP), other- wise revealed as a safe approach, has recently been associ-
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