Donor-derived acute myeloid leukemia in solid organ transplantation

Area of Science:

• Oncology
• Transplantation Medicine
• Genomics

Background:

• Solid organ transplantation can transmit diseases, including malignancies, posing risks to recipients.
• Acute myeloid leukemia (AML) transmission via organ donation is rare and poorly understood.
• Previous cases lacked comprehensive molecular and genomic investigation.

Purpose of the Study:

• To investigate the genomic basis of AML transmission from a deceased donor to solid organ recipients.
• To analyze the molecular evolution of donor-derived AML in different recipient environments.
• To identify potential mechanisms of tumor escape and inform future prevention strategies.

Main Methods:

• Review of medical records for liver and kidney recipients.
• Microsatellite analysis to confirm donor chimerism.
• Targeted molecular analysis for specific gene mutations (NPM1, FLT3).
• Whole exome sequencing (WES) for comprehensive genomic profiling.

Main Results:

• AML was transmitted from the donor to two kidney recipients and one liver recipient.
• Donor-derived AML showed distinct clonal evolution in each recipient.
• NPM1 mutation was present in the donor and all recipients; FLT3 mutation was unique to one kidney recipient.
• WES identified additional mutations and HLA genomic loss, particularly in the relapsed kidney recipient.

Conclusions:

• This is the first in-depth genomic analysis of AML transmission via solid organ transplantation.
• Distinct molecular evolution patterns were observed in recipients, influencing disease progression and treatment response.
• Genomic insights provide a potential explanation for tumor escape and highlight the need for improved donor screening.