Increased Expression of CD56 on Plasmacytoid Dendritic Cells in Myeloid Leukemia Associated with Down Syndrome (ML-DS) Is Normal Regeneration and Not Measurable Residual Disease

Introduction: It has long been known that Down syndrome is associated with an increased risk for hematologic malignancies. One such disease is myeloid leukemia associated with Down syndrome (ML-DS), a disease that almost always occurs during the first 5 years of life. As research on ML-DS has progressed, understanding has grown that after the initiation of therapy, the non-neoplastic myeloid progenitor cells in ML-DS patients have a characteristic immunophenotype with the expression of CD56 on a subset of the CD34+ myeloid progenitor cells being one of the most notable features. The discovery that this immunophenotype is normal in ML-DS patients post-therapy has been of the utmost importance as it has led to such patients being properly classified as being negative for measurable residual disease. Plasmacytoid dendritic cells (pDCs) are another cell type in which CD56 expression is often part of the neoplastic immunophenotype, and we hypothesized that CD56 may also be differentially expressed in ML-DS pDCs post-therapy. Herein, we investigated the immunophenotype of pDCs in ML-DS patients found to be negative for measurable residual disease. Methods: A total of 10 bone marrow specimens from ML-DS patients post-treatment initiation and 7 bone marrow specimens from patients that did not have DS, were aged 0-4 years (matching the age range of ML-DS), had a myeloid neoplasm and were post-treatment initiation (non-DS) were included in this study. All specimens were found to be negative for measurable residual disease by difference from normal (ΔN) flow cytometry (the gold standard for the determination of residual disease in the Children's Oncology Group 1531 study on ML-DS) and were evaluated for CD56 and CD303 expression on pDCs. pDCs were defined as HLA-DR+/CD123++ (high intensity). Results: As expected, the ML-DS patients had a significantly greater percentage of CD34+CD56+ myeloid progenitor cells than the non-DS group, both in terms of percent total non-erythroid cells (0.9% vs 0.006%, P