AFF1 explained

AF4/FMR2 family member 1 is a protein that in humans is encoded by the AFF1 gene.^{[1] [2] [3] [4]} At its same location was a record for a separate PBM1 gene, which has since been withdrawn and considered an alias. It was previously known as AF4 (ALL1-fused gene from chromosome 4).

The gene is a member of the AF4/FMR2 (AFF) family, a group of nuclear transcriptional activators which encourage RNA elongation. It is a component of the super elongation complex.^[5] It is recognized as a proto-oncogene: chromosomal translocations associated with leukemia can fuse this gene with others like KMT2A, producing an uncontrolled activator protein.^[1]

Further reading

• Morrissey J, Tkachuk DC, Milatovich A, Francke U, Link M, Cleary ML . A serine/proline-rich protein is fused to HRX in t(4;11) acute leukemias . Blood . 81 . 5 . 1124–31 . March 1993 . 8443374 . 10.1182/blood.V81.5.1124.1124. free .
• Nakamura T, Alder H, Gu Y, Prasad R, Canaani O, Kamada N, Gale RP, Lange B, Crist WM, Nowell PC . Genes on chromosomes 4, 9, and 19 involved in 11q23 abnormalities in acute leukemia share sequence homology and/or common motifs . Proceedings of the National Academy of Sciences of the United States of America . 90 . 10 . 4631–5 . May 1993 . 8506309 . 46566 . 10.1073/pnas.90.10.4631 . 1993PNAS...90.4631N . free .
• Frestedt JL, Hilden JM, Kersey JH . AF4/FEL, a gene involved in infant leukemia: sequence variations, gene structure, and possible homology with a genomic sequence on 5q31 . DNA and Cell Biology . 15 . 8 . 669–78 . August 1996 . 8769569 . 10.1089/dna.1996.15.669 .
• Nilson I, Reichel M, Ennas MG, Greim R, Knörr C, Siegler G, Greil J, Fey GH, Marschalek R . Exon/intron structure of the human AF-4 gene, a member of the AF-4/LAF-4/FMR-2 gene family coding for a nuclear protein with structural alterations in acute leukaemia . British Journal of Haematology . 98 . 1 . 157–69 . July 1997 . 9233580 . 10.1046/j.1365-2141.1997.1522966.x . 25176760 . free .
• Megonigal MD, Rappaport EF, Jones DH, Kim CS, Nowell PC, Lange BJ, Felix CA . Panhandle PCR strategy to amplify MLL genomic breakpoints in treatment-related leukemias . Proceedings of the National Academy of Sciences of the United States of America . 94 . 21 . 11583–8 . October 1997 . 9326653 . 23546 . 10.1073/pnas.94.21.11583 . 1997PNAS...9411583M . free .
• Felix CA, Kim CS, Megonigal MD, Slater DJ, Jones DH, Spinner NB, Stump T, Hosler MR, Nowell PC, Lange BJ, Rappaport EF . Panhandle polymerase chain reaction amplifies MLL genomic translocation breakpoint involving unknown partner gene . Blood . 90 . 12 . 4679–86 . December 1997 . 9389682 . 10.1182/blood.V90.12.4679. free .
• Isnard P, Depetris D, Mattei MG, Ferrier P, Djabali M . cDNA cloning, expression and chromosomal localization of the murine AF-4 gene involved in human leukemia . Mammalian Genome . 9 . 12 . 1065–8 . December 1998 . 9880680 . 10.1007/s003359900927 . 29956410 .
• Felix CA, Hosler MR, Slater DJ, Megonigal MD, Lovett BD, Williams TM, Nowell PC, Spinner NB, Owens NL, Hoxie J, Croce CM, Lange BJ, Rappaport EF . Duplicated regions of AF-4 intron 4 at t(4;11) translocation breakpoints . Molecular Diagnosis . 4 . 4 . 269–83 . December 1999 . 10671636 . 10.1016/S1084-8592(99)80002-2 .
• Reichel M, Gillert E, Breitenlohner I, Angermüller S, Fey GH, Marschalek R, Repp R, Greil J, Beck JD . Rapid isolation of chromosomal breakpoints from patients with t(4;11) acute lymphoblastic leukemia: implications for basic and clinical research . Leukemia . 15 . 2 . 286–8 . February 2001 . 11236948 . 10.1038/sj.leu.2402018 . 42706811 .
• Raffini LJ, Slater DJ, Rappaport EF, Lo Nigro L, Cheung NK, Biegel JA, Nowell PC, Lange BJ, Felix CA . Panhandle and reverse-panhandle PCR enable cloning of der(11) and der(other) genomic breakpoint junctions of MLL translocations and identify complex translocation of MLL, AF-4, and CDK6 . Proceedings of the National Academy of Sciences of the United States of America . 99 . 7 . 4568–73 . April 2002 . 11930009 . 123688 . 10.1073/pnas.062066799 . 2002PNAS...99.4568R . free .
• Bertrand FE, Spengeman JD, Shah N, LeBien TW . B-cell development in the presence of the MLL/AF4 oncoprotein proceeds in the absence of HOX A7 and HOX A9 expression . Leukemia . 17 . 12 . 2454–9 . December 2003 . 14562113 . 10.1038/sj.leu.2403178 . 10639425 .
• Caslini C, Serna A, Rossi V, Introna M, Biondi A . Modulation of cell cycle by graded expression of MLL-AF4 fusion oncoprotein . Leukemia . 18 . 6 . 1064–71 . June 2004 . 14990976 . 10.1038/sj.leu.2403321 . 19189264 .
• Bursen A, Moritz S, Gaussmann A, Moritz S, Dingermann T, Marschalek R . Interaction of AF4 wild-type and AF4.MLL fusion protein with SIAH proteins: indication for t(4;11) pathobiology? . Oncogene . 23 . 37 . 6237–49 . August 2004 . 15221006 . 10.1038/sj.onc.1207837 . 9645787 . free .
• Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier JM . Functional proteomics mapping of a human signaling pathway . Genome Research . 14 . 7 . 1324–32 . July 2004 . 15231748 . 442148 . 10.1101/gr.2334104 .
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP . Large-scale characterization of HeLa cell nuclear phosphoproteins . Proceedings of the National Academy of Sciences of the United States of America . 101 . 33 . 12130–5 . August 2004 . 15302935 . 514446 . 10.1073/pnas.0404720101 . 2004PNAS..10112130B . free .
• Xia ZB, Popovic R, Chen J, Theisler C, Stuart T, Santillan DA, Erfurth F, Diaz MO, Zeleznik-Le NJ . The MLL fusion gene, MLL-AF4, regulates cyclin-dependent kinase inhibitor CDKN1B (p27kip1) expression . Proceedings of the National Academy of Sciences of the United States of America . 102 . 39 . 14028–33 . September 2005 . 16169901 . 1236570 . 10.1073/pnas.0506464102 . free .

Notes and References

1. Domer PH, Fakharzadeh SS, Chen CS, Jockel J, Johansen L, Silverman GA, Kersey JH, Korsmeyer SJ . Acute mixed-lineage leukemia t(4;11)(q21;q23) generates an MLL-AF4 fusion product . Proceedings of the National Academy of Sciences of the United States of America . 90 . 16 . 7884–8 . August 1993 . 7689231 . 47247 . 10.1073/pnas.90.16.7884 . 1993PNAS...90.7884D . free .
2. Gu Y, Nakamura T, Alder H, Prasad R, Canaani O, Cimino G, Croce CM, Canaani E . The t(4;11) chromosome translocation of human acute leukemias fuses the ALL-1 gene, related to Drosophila trithorax, to the AF-4 gene . Cell . 71 . 4 . 701–8 . November 1992 . 1423625 . 10.1016/0092-8674(92)90603-A . 6257922 .
3. Chen CS, Hilden JM, Frestedt J, Domer PH, Moore R, Korsmeyer SJ, Kersey JH . The chromosome 4q21 gene (AF-4/FEL) is widely expressed in normal tissues and shows breakpoint diversity in t(4;11)(q21;q23) acute leukemia . Blood . 82 . 4 . 1080–5 . August 1993 . 10.1182/blood.V82.4.1080.bloodjournal8241080 . 31 January 2024 . 8353274 . free .
4. Web site: Entrez Gene: AFF1 AF4/FMR2 family, member 1.
5. Melko M, Douguet D, Bensaid M, Zongaro S, Verheggen C, Gecz J, Bardoni B . Functional characterization of the AFF (AF4/FMR2) family of RNA-binding proteins: insights into the molecular pathology of FRAXE intellectual disability . Human Molecular Genetics . 20 . 10 . 1873–85 . May 2011 . 21330300 . 10.1093/hmg/ddr069 . free .