Aff1, also known as AF4/FMR2 family member 1, is a central scaffolding protein of the super elongation complex (SEC). It plays a crucial role in regulating gene transcription, which is essential for various biological processes [1,3,4,5,6]. The SEC, with Aff1 as a key component, is involved in controlling transcription elongation, and Aff1 has been associated with different cellular differentiation processes and disease conditions [1,3,4,5,6]. Genetic models, such as gene knockout (KO) and conditional knockout (CKO) mouse models, can be valuable for studying Aff1's functions.

In adipogenic differentiation, depletion of Aff1 in human mesenchymal stromal/stem cells (hMSCs) and 3T3-L1 pre-adipocytes enhanced adipogenesis, while overexpression of Aff1 in 3T3-L1 cells reduced adipogenic differentiation and adipose tissue formation in vivo. Mechanistically, Aff1 binds to the promoter region of the Tgm2 gene and regulates its transcription, and overexpression of Tgm2 rescues adipogenic differentiation of Aff1-deficient cells [1]. In osteogenic differentiation, siRNA-mediated depletion of Aff1 in human MSCs led to increased alkaline phosphatase (ALP) activity, enhanced mineralization, and up-regulated expression of osteogenic-related genes [4].

In conclusion, Aff1 plays an inhibitory role in adipogenic and osteogenic differentiations. These functions of Aff1, as revealed through model-based research, contribute to our understanding of cell differentiation processes. Additionally, in neonatal leukemia, the t(4;11)(q21.3;q23.3)/KMT2A-AFF1 rearrangement is the most frequently observed cytogenetic/molecular abnormality, highlighting the importance of Aff1-related research in understanding this disease [2].