Disease relevance of AFF3

• We showed that the LAF4 gene on 2q11.2-12 was fused to the MLL gene on 11q23 in a pediatric patient with CD10 positive acute lymphoblastic leukemia (ALL) having t(2;11)(q11;q23) [1].
• In a group of 64 primary human breast tumors, we found that LAF-4 was overexpressed in approximately 20% of the cases [2].

High impact information on AFF3

• A novel human gene, LAF-4, was isolated from a subtracted cDNA library that showed strong sequence similarity to AF-4, a gene that is translocated in t(4;11)(q21;q23) acute lymphoblastic leukemias (ALLs) [3].
• In mouse tissues, LAF-4 mRNA was found to be present at highest levels in lymphoid tissues, present at lower levels in brain and lung, and absent from other tissues [3].
• In human and mouse lymphoid cell lines, LAF-4 expression was highest in pre-B cells, intermediate in mature B cells, and absent in plasma cells, thus pointing to a potential regulatory role for LAF-4 in lymphoid development [3].
• These findings suggest that LAF4, AF4 and AF5q31 might define a new family particularly involved in the pathogenesis of 11q23-associated ALL [1].
• The LAF4 gene, which encodes a lymphoid nuclear protein of 1227 amino acids with transactivation potential, is thought to have a role in early lymphoid development [1].

Biological context of AFF3

• Rapid amplification of cDNA ends-polymerase chain reaction (PCR) and reverse transcriptase-PCR identified the LAF4 gene mapped on chromosome region 2q11.2-q12 as a fusion partner of the MLL gene [4].
• Our results suggest that LAF-4 may be a proto-oncogene that is transcriptionally activated in some cases of breast cancer [2].
• Although epigenetic changes may be involved in altered expression of some genes, differences in LAF-4 expression were not associated with DNA methylation of the predicted promoter region [2].
• The LAF4 gene was identified previously by its high sequence homology to the AF4 protein and encodes a protein of 1,227 amino acids [4].
• Occurrence of an MLL/LAF4 fusion gene caused by the insertion ins(11;2)(q23;q11.2q11.2) in an infant with acute lymphoblastic leukemia [5].

Anatomical context of AFF3

• LAF4 expression was found to be higher in ALL cell lines than in AML and Epstein-Barr virus-transformed B-lymphocyte cell lines [1].
• However, 2 of 5 breast cancer cell lines were found to express LAF-4 at both the RNA and protein levels [2].
• In line with the previous finding that LAF-4 expression is tissue specific, we did not detect any LAF-4 mRNA in normal mammary epithelial cell lines [2].

Other interactions of AFF3

• Comparison of AF-4 protein coding sequences with the LAF-4 and FMR-2 sequences revealed five highly conserved domains of potential functional relevance [6].

Analytical, diagnostic and therapeutic context of AFF3

• Antibodies to LAF-4 showed it to be a nuclear protein that showed an uneven, granular immunofluorescence pattern [3].
• Using RNA in situ hybridization, we demonstrated that LAF-4 is expressed in mammary tumor cells but not in normal acini [2].

References