Block of differentiation by disruption of hematopoietic transcription factors in myeloid and lymphoid leukemia. Depicts the molecular mechanisms leading to disruption of the transcription factor CCAAT/enhancer binding protein alpha (C/EBPα) in myeloid leukemia and the paired box gene 5 (Pax5) in lymphocytic leukemia. Disruption of these transcription factors blocks hematopoietic cells in their early stages of differentiation. Treatment with substances altering the epigenetic settings such as histone deacetylase inhibitors or demethylating agents may partly overcome the block in differentiation. Forced expression of the normal counterpart of the disrupted transcription factor can often re-establish differentiation. In the future, synthesis of small molecules specifically targeting transcription factors or nuclear reprogramming and gene therapy may provide useful tools for correcting defective differentiation in hematologic malignancies.