CD123 Expression in Acute Myeloid Leukemia: A Prognostic Marker for MRD and Relapse in FLT3-ITD Mutations

This study investigates the role of CD123, a marker for leukemia stem cells (LSC), in acute myeloid leukemia (AML) and its association with minimal residual disease (MRD) and disease recurrence. The research involved 95 AML patients and analyzed CD123 expression on CD34+ blast cells. It was found that higher CD123 expression correlated with poor prognosis indicators and was a significant factor in MRD status and time to relapse.

In the study, CD123 was highly expressed in bone marrow samples at diagnosis, and its higher presence on blasts and CD34+ stem/progenitor cells was linked to unfavorable cytogenetics and unmutated NPM1. A substantial number of patients achieved negative MRD, which strongly correlated with a longer time to relapse. A higher proportion of CD123+CD34+ cells during remission was associated with a higher risk of remaining MRD-positive.

Furthermore, the study examined CD123 expression in the LSC fraction of AML bone marrow samples and compared it with normal bone marrow samples. The frequency of CD123+ cells was significantly higher in AML samples, especially in those with FLT3 mutations. These CD123+ LSCs with FLT3-ITD exhibited heightened activity in multiple intracellular signaling pathways.

The findings suggest that targeting CD123-expressing LSCs could be an effective therapeutic strategy in AML, particularly for those with FLT3 mutations, due to the significant expression of CD123 and the activation of key signaling pathways in these cells.