The promiscuous MLL gene links chromosomal translocations to cellular differentiation and tumour tropism

Translocation t(6;14) as the Sole Chromosomal Abnormality in Adenoid Cystic Carcinoma of the Base of Tongue

“…These translocations are believed to result in activation of oncogenes or the formation of fusion genes that induce malignant transformation of a committed progenitor cell [27]. In that context, balanced promiscuous translocations may lead to the formation of phenotypically similar tumors of different clinical outcomes and therapeutic sensitivities [30]. Since the translocations in our case and in all previously reported ACCs involving chromosome 6q were exclusively balanced in nature and limited to a few breakpoints and chromosomal partners, we contend that an activated oncogene or a fusion gene is likely underlying the development of at least a subset of ACC [3,4,7,8,11].…”

A diagnostic biochip for the comprehensive analysis of MLL translocations in acute leukemia

“…These aberrations usually occur in tumors of specific hematological lineages, and suggest a crucial role for MLL in determining disease phenotype or tumor tropism. 5 Most of the genomic breakpoints occur in a clustered region between exons 5 and 11 in an 8 kb genomic region, but some rearrangements have been recently observed outside this region in adult T-ALL. 6 More than 30 different partners resulting in various MLL FG transcripts have been identified (Table 1).…”

“…2,11 For instance, MLL-AF9 is primarily found in AML, and translocation involving the AF4 gene occurs almost exclusively in B-cell lineage tumors. 5 The most common partners are AF4 in pro-B ALL and AF9 in AML, mainly M5, accounting for 40 and 27% of the 11q23 translocations, respectively. 11 19p13 is another frequently encountered rearrangement observed in approximately 12% of 11q23 translocations in both ALL and AML.…”

B-cell development in the presence of the MLL/AF4 oncoprotein proceeds in the absence of HOX A7 and HOX A9 expression

“…In conventional t(4;11), MLL/AF4 leads to transformation, consistent with studies demonstrating that truncated MLL is sufficient for transformation. 19,20 The presence The HOX C8 promoter is activated in the presence of the BLIN-3 MLL/AF4 fusion gene. Luciferase assays were performed as described in Materials and methods.…”

“…12 Although the contribution of MLL/AF4 to leukemogenesis is not precisely defined, MLLlacZ fusions are sufficient to confer oncogenesis in mice, supporting a gain of function role for MLL in neoplastic transformation. 19,20 Downstream targets of MLL/AF4 are just beginning to be identified, but HOX A7 and HOX A9 have been implicated as targets for dysregulation in MLL-mediated oncogenesis. [21][22] HOX genes play a pivotal role in hematopoietic lineage commitment and differentiation.…”