Disease relevance of MLLT6

• Expression of AF17 was significantly enhanced in 8 of the 12 colorectal cancer tissues examined [1].
• The t(11;17) has been described in patients with acute myeloid leukemia (AML), and the AF17 gene was previously cloned as a fusion partner of the MLL gene in t(11;17)(q23;q21)-AML [2].
• In the experiments reported here, analysis by cDNA microarray indicated that AF17, a fusion partner of the MLL gene in acute leukemias with t(11;17)(q23;q21), was transactivated according to accumulation of beta-catenin [1].
• Acute myelocytic leukemia with t(11;17)(q23;q12-q21) involves a fusion of MLL and AF17 [3].

High impact information on MLLT6

• The first part of the zinc finger region of CEZF has strong similarity to the corresponding regions of AF10 (66%) and MLLT6 (64%) at the cDNA level [4].
• To begin studying this, we examined the All1, AF4, AF9, and AF17 proteins for the presence of potential transcriptional regulatory domains [5].
• Here we report the cloning and characterization of the ALL-1 partner at 17q21, the AF17 gene [6].
• The AF17 gene encodes a protein of 1093 amino acids, containing a leucine-zipper dimerization motif located 3' of the fusion point and a cysteine-rich domain at the N terminus [6].
• These structures have been found to be conserved in sequence and position in three other proteins, AF17, BR140, and a previously unrecognized Caenorhabditis elegans gene, provisionally named CEZF [7].

Biological context of MLLT6

• The MLL-MLLT6/AF17 transcripts were extremely heterogeneous and the detection of seven different in-frame transcript and splice variants enabled us to predict the protein domains relevant for leukemogenesis [8].
• Gene BR140, which is related to AF10 and AF17, maps to chromosome band 3p25 [9].
• Introduction of a plasmid designed to express AF17 stimulated growth of NIH3T3 cells, and fluorescence-activated cell sorter analysis indicated that the AF17 regulation of cell-cycle progression was occurring mainly at the G(2)-M transition [1].
• The fact that 2 forms of MLL-AF17 retain the leucine zipper domain of AF17 suggests that the dimerization domain of AF17 is critical for leukemogenesis by the MLL-AF17 fusion gene [10].
• There was no sex difference in AF 17 alpha-OH-progesterone levels, nor any significant downward trend in concentrations throughout the observed gestation period [11].

Analytical, diagnostic and therapeutic context of MLLT6

• Although the previously reported form of the MLL-AF17 fusion transcript was not detected by reverse transcriptase-polymerase chain reaction (PCR) analysis, a novel form of an MLL-AF17 fusion transcript joining MLL exon 6 to AF17 exon 9 was detected by complementary DNA panhandle PCR [10].
• The three subjects with high AF 17 alpha-OH-progesterone levels delivered babies affected with CAH, although HLA-typing in one case was non-conclusive [11].

References