The Mixed Lineage Leukemia (MLL) gene is frequently rearranged in leukemia, especially in infantile leukemia and therapy-related leukemia. The MLL gene is localized at chromosome 11q23, and is involved in almost all of the chromosomal translocations involving 11q23. Twenty-four fusion partner genes have been identified to date, and the N-terminus of MLL fuses in-frame to the partner genes in all cases. Some of the MLL fusion partner genes encode transcription factors; others encode small GTP binding protein interacting molecules or cytoplasmic proteins, the functions of which are presently unknown. As a result of the diverse features of the MLL fusion partners, the underlying mechanism for leukemogenesis remains obscure. We cloned the MLL fusion partner gene from leukemic cells from a therapy-related leukemia patient with t(3;11)(p21;q23) and designated the gene AF3p21. This patient had a long latency period (9 years) before developing secondary leukemia. The AF3p21 gene encodes a nuclear protein with a molecular mass of 80 kDa, and this protein has SH3 and proline-rich domains. Among MLL fusion partners identified to date, only AF10 and AF17 have a homo-oligomerization domain. AF3p21 also has a homo-oligomerization domain, which was revealed by using a mammalian two-hybrid system. These results suggest that one possible role of the MLL fusion partners is to form an oligomer of truncated MLL. In this review, current knowledge about MLL-involved leukemogenesis is outlined.