MLL/AF4

Chromosomal region 11q23 is frequently rearranged in acute leukemias. The nature of rearrangements is mostly balanced translocations, but also includes unbalanced translocations, inversions, insertions, and tandem duplications. The MLL gene – a transcriptional regulator – resides in this region, and is frequently involved in reciprocal exchanges with various partner genes. One of the most common rearrangements is t(4;11)(q21;q23), in which a chimeric oncogene is formed between MLL and its translocation partner AF4. The t(4;11)(q21;q23) translocation is present in approximately 10% of acute lymphoblastic leukemia (ALL) patients; most frequently in infant leukemia where it is observed over 80%. The t(4;11)(q21;q23) translocation has also been associated with treatment related leukemia (secondary to epipodophyllotoxins). Different breakpoints in the genes result in multiple MLL-AF4 mRNA products with different sizes. It is important to perform molecular diagnostic screening for the presence of t(4;11), along with t(9;22), t(12;21) and t(1;19) in pediatric ALL to determine prognosis and therapeutic approaches.