ML-DS: A Unique Condition for Measurable Residual Disease Detection

Children with Down syndrome (DS) have an increased risk of developing myeloid leukemia of Down syndrome (ML-DS). This disease is preceded by a self-limiting, preleukemic condition known as transient myeloproliferative disease (TMD). While most DS neonates with TMD will spontaneously resolve without treatment, 10–20% of these TMD cases will later evolve into ML-DS. The specific mechanisms leading to leukemic transformation and relapse in ML-DS remain to be elucidated. Furthermore, DS hematopoietic cells present a distinct antigenic profile which limits the current best practice for residual disease detection in acute myeloid leukemia: a multidimensional flow cytometric assay comparing against a set of normal immunophenotype. Recent advances in high-throughput sequencing now offer a novel alternative to these traditional methods for residual detection and promise to broaden our understanding of the molecular mechanisms in this unique disease.