Detection of clonal selection by multicolor flow cytometry in TAM with multiple GATA1 mutations

Transient abnormal myelopoiesis (TAM) occurs in approximately 10% of neonates with Down syndrome (DS), and about 20% of these cases progress to myeloid leukemia associated with DS (ML-DS) within the first four years of life. TAM usually arises from a single clone harboring an identical GATA1 mutation, but approximately 8% of cases carry heterogeneous clones with distinct GATA1 mutations. To date, no reliable method has been established to determine which clone progresses to ML-DS. Here, we report a unique TAM case with multiple distinct GATA1 mutations in which a minor clone at the time of diagnosis evolved into overt ML-DS by 59 days of age. It is particularly noteworthy that changes in blast surface marker expression detected by flow cytometry (FCM) following a single course of low-dose cytarabine coincided with the emergence of the leukemogenic clone. This case illustrates that the use of FCM may serve as a valuable tool for the early detection of leukemogenic clonal expansion in TAM patients harboring multiple GATA1 mutations.