Telomere shortening in donor cell-derived acute promyelocytic leukemia after allogeneic hematopoietic stem cell transplantation: a case report

Donor cell leukemia (DCL), in which malignancy evolves from donor's stem cells, is an infrequent complication of allogeneic hematopoietic stem cell transplantation. Acute promyelocytic leukemia (APL) derived from donor cell is extremely rare and only four cases have been reported to date. Herein we report a case of donor cell-derived APL developing 32 months after haploidentical peripheral blood stem cell transplantation using posttransplant cyclophosphamide for myelodysplastic syndromes. Donor origin of APL cells was validated by conventional karyotyping, florescence in situ hybridization, and single-nucleotide polymorphisms-based chimerism analysis. Targeted sequencing of both the donor and the recipient demonstrated newly-acquired PML::RARA fusion only in the recipient's cells after transplantation, without additional genetic abnormalities. The telomere length was measured at multiple timepoints before and after transplantation. The analysis revealed markedly shortened telomere length at APL onset, which reflect both stem cell expansion following transplantation and expansion of APL cells. Our first-ever report of telomere dynamics in DCL cases provides evidence for the involvement of telomere attrition in DCL pathogenesis.