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.