Molecular studies reveal and gene fusions displaced in a case of infantile acute lymphoblastic leukemia with complex karyotype.

The present report describes a unique infantile acute lymphoblastic leukemia (ALL) case with cryptic mixed-lineage leukemia (MLL) rearrangements with 11q23 chromosomal translocation. break-apart signals were identified by fluorescence hybridization, and transcriptome sequencing revealed -myeloid/lymphoid or mixed-lineage leukemia; translocated To, 10 ()/ fusion transcripts. Analysis also revealed a previously unreported /-homeobox protein Mohawk () transcript, where the 5' portion of at 10p12.31 was fused out-of-frame with the 3' portion of at 10p12.1, which is closely located to /. Furthermore, the reciprocal 3'- gene segment was fused in-frame to AT-rich interaction domain () at 10q21. Previously, common allelic variants in , which are directly associated with hematopoietic differentiation and development, have been repeatedly and significantly associated with childhood ALL. The heterozygous genotype in (RefSNP: rs10821936) increased the risk for leukemia with -rearrangement. In particular, single nucleotide polymorphisms of conferred increased risk for . Based on these findings, the authors propose that while the presence of reciprocal alleles has been detected in this patient, different pathological disease mechanisms may be at play due to individual recombination events.