When Standard Markers Are Not Sufficient for Monitoring Minimal Residual Disease or Targeted Treatment: New Transcriptome Derived Flow Cytometry Markers for Switching B Cell Precursor Leukemias

Switching from B to monocytic lineage is more frequent than expected (4-6% out of all pediatric B cell precursor leukemias (BCP ALLs), called swALL). SwALLs frequently contain CD2 aberrant expression and ERG gene deletions. Recently described subtype characterized by rearrangement of DUX4 gene overlaps with swALL. The B-to-monocytoid switching can be missed by current flow cytometry (FC) antibody panels. The search for better FC markers is of clinical importance also in the context of switching occurring under CD19 directed therapies (blinatumomab or CAR T cells). The malignant potential of switched blasts is not clear, there is an evidence that part of the patients might suffer from relapse corresponding to BCP ALL. However, the relapse corresponding to switched monocytic blasts was also observed. We performed RNA sequencing of swALL diagnostic blasts (n=31), intermediate cells co-expressing B cell and monocytic markers (n=3) and switched monocytic blasts (n=6, clonal relatedness was confirmed by identification of identical Ig-TCR rearrangements with initial BCP ALL clone), control BCP ALLs (n=50), monocytic AMLs (n=5, MLL rearranged 3, CBFb/MYH11 2) and healthy monocytes sorted from blood (n=3) to answer following questions: