AFF1 (ALF transcription elongation factor 1) is a scaffolding protein that functions as a key component of the super elongation complex (SEC), linking positive elongation factor b (P-TEFb) and ELL1/2 to regulate transcriptional elongation and chr4 remodeling 1. The protein plays critical roles in cellular differentiation processes, particularly in osteogenic differentiation of mesenchymal stem cells, where AFF1 depletion enhances osteogenic potential by regulating DKK1 expression through direct promoter binding 1. However, AFF1 is perhaps most clinically significant due to its involvement in leukemia pathogenesis. The t(4;11)(q21.3;q23.3)/KMT2A-AFF1 translocation is the most frequently observed cytogenetic abnormality in neonatal leukemia and represents a major oncogenic driver in acute lymphoblastic leukemia 2. This fusion creates a chimeric oncogene where the N-terminal KMT2A is joined to C-terminal AFF1, resulting in aberrant transcriptional regulation 3. KMT2A-AFF1 rearranged leukemias are associated with poor prognosis and high relapse rates, particularly in infant and adult B-cell precursor ALL 4 5. The HOXA-type AFF1 subgroup (IC5) identified in infant ALL represents one of five distinct molecular clusters with different developmental stages and therapeutic responses 6. This makes AFF1 fusions important targets for emerging menin inhibitor therapies in leukemia treatment 3.