A pro B cell population forms the apex of the leukemic hierarchy in Hoxa9/Meis1-dependent AML

In the murine HoxA9/Meis1 (H9M) AML model leukemic stem cell (LSC) potential lies in three different heterogeneous immunophenotypes including Lin-cKit+ progenitor cells (Lin-), Gr1+CD11b+cKit+ myeloid cells and lymphoid cells (Lym+). We performed Bulk-RNA sequencing to reveal differences in the transcriptional program between Lin- and Lym+ cells. Therefore, Lin- and Lym+ cells of secondary AML mouse bone marrow was isolated and sequenced. We could identify potential lymphoid master regulators that correlated with lymphoid cell development and presumably aggressive disease. In total, 6 bone marrow samples from 6 secondary transplanted HoxA9/Meis1 mice were anaylzed. 3 samples contained lymphoid leukemic stem cells (LSCs) from mice that were transplantaed with lymphoid LSCs. The other 3 samples contained Lin- LSCs from mice transplanted with Lin- LSCs