RS4:11 Cells

The RS4:11 cell line is derived from a 32-year-old female patient with relapsed acute lymphoblastic leukemia (ALL) characterized by the t(4:11)(q21:q23) chromosomal translocation. This translocation results in the formation of the **KMT2A-AFF1 (formerly MLL-AF4)** fusion gene, which is a hallmark of this leukemia subtype. RS4:11 cells exhibit a biphenotypic profile, co-expressing both B-cell and monocytic markers, reflecting the mixed-lineage characteristics associated with this genetic rearrangement. The cell line is widely used as a model for understanding the biology of KMT2A-rearranged leukemias, which are associated with aggressive disease and poor prognosis.

RS4:11 cells display features typical of pre-B lymphoblasts, including expression of markers such as CD19, HLA-DR, and terminal deoxynucleotidyl transferase (TdT), along with rearranged immunoglobulin heavy and light chain genes. Interestingly, upon treatment with differentiation-inducing agents like phorbol esters, RS4:11 cells adopt a monocyte-like phenotype, highlighting their lineage plasticity. This characteristic makes the cell line particularly valuable for studying the molecular drivers of differentiation and lineage commitment in leukemia.

Genetically, the t(4:11) translocation disrupts the **KMT2A gene at 11q23**, fusing it with **AFF1 (AF4)** on 4q21, leading to a chimeric protein that aberrantly regulates gene expression, including Hox genes involved in hematopoietic development. RS4:11 cells have also been used to study secondary mutations, such as those in **FLT3**, which contribute to leukemogenesis and treatment resistance. The cell line serves as a robust preclinical model for testing targeted therapies, including inhibitors of the KMT2A-AFF1 interaction and agents aimed at associated signaling pathways.