Infant acute lymphoblastic leukemia B (B-ALL) accounts for 10% of childhood ALL. Eighty percent of infant B-ALL was caused by MLL gene rearrangement (MLL-r). The overall survival rate of ALL was less than 35% in infants with MLL-r. Among infant ALL with MLL-r, infants with positivefusion gene MLL-AF4 (MA4) formed by chromosome t (4;11) had even poor prognosis. Studies in monozygotic twins and archived blood spot at birth had verified that fusion gene MA4 originated from antenatal. Whole genome sequencing found that t (4;11) alone might be sufficient to spawn leukemia. This paper is going to summarize the advances in biological characteristics such as clinical features, cellular origin, genomics and disease models of  normal MLL gene and infant  B-ALL with MA4.