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Gene Review

MLLT10  -  myeloid/lymphoid or mixed-lineage leukemia...

Homo sapiens

Synonyms: AF10, ALL1-fused gene from chromosome 10 protein, Protein AF-10
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Disease relevance of MLLT10


High impact information on MLLT10

  • RNA was examined from fresh human B cells stimulated to IgE production by interleukin 4 plus anti-CD40, as well as from the human IgE-producing line AF10 [6].
  • Using a combination of positional cloning and candidate gene approach, we cloned the breakpoint and were able to show that AF10 is fused to a novel gene that we named CALM (Clathrin Assembly Lymphoid Myeloid leukemia gene) located at 11q14 [7].
  • AF10, a putative transcription factor, had recently been cloned as one of the fusion partners of MLL [7].
  • The identification of the CALM/AF10 fusion gene in the widely used U937 cell line will contribute to our understanding of the malignant phenotype of this line [7].
  • The t(10;11)(p13;q14) in the U937 cell line results in the fusion of the AF10 gene and CALM, encoding a new member of the AP-3 clathrin assembly protein family [7].

Biological context of MLLT10

  • 10;11 rearrangements require at least three breaks in order to generate an in-frame MLL-MLLT10 fusion as a result of the opposite orientations of both genes on the respective chromosome arms [8].
  • We observed an as yet unreported chromosomal mechanism with at least four breakpoints, leading to MLL-MLLT10 gene fusion in a 24-year-old male [8].
  • In this study, we describe a detailed molecular cytogenetic analysis of MLL-MLLT10 positive 10;11 rearrangements in two patients [8].
  • The AF10 gene encodes a putative transcription factor containing an N-terminal LAP/PHD zinc finger motif, a functional nuclear localization signal, an AT-hook domain, and a leucine zipper toward the C-terminus [2].
  • Interphase fluorescence in situ hybridization (FISH) was performed with 2 YACs flanking the CALM region, a YAC contig of the MLL region, and a YAC spanning the AF10 breakpoint [9].

Anatomical context of MLLT10


Associations of MLLT10 with chemical compounds

  • The AF10 leucine zipper is required for leukemic transformation of myeloid progenitors by MLL-AF10 [13].
  • A consistent feature of these fusions was the juxtaposition of the leucine dimerization motif of AF10 onto the NH2-terminal region of HRX [14].
  • However, two partner genes, AF10 and AF17 are related through the presence of a cysteine rich region and a leucine zipper [15].
  • The mutation was mapped to a Drosophila homolog of human AF10/AF17 leukemia fusion genes (alf), and therefore named Dalf [16].
  • Using AF10 cells, whose growth was determined to be mediated by the autocrine action of IL-6, we found that RA reduction of IL-6R was concentration-dependent over a range of 10(-11) to 10(-5) M and corresponded to the ability of the retinoid to inhibit cell proliferation [17].

Other interactions of MLLT10


Analytical, diagnostic and therapeutic context of MLLT10


  1. MLL-MLLT10 fusion in acute monoblastic leukemia: variant complex rearrangements and 11q proximal breakpoint heterogeneity. Morerio, C., Rapella, A., Rosanda, C., Lanino, E., Lo Nigro, L., Di Cataldo, A., Maserati, E., Pasquali, F., Panarello, C. Cancer Genet. Cytogenet. (2004) [Pubmed]
  2. The MLL fusion partner AF10 binds GAS41, a protein that interacts with the human SWI/SNF complex. Debernardi, S., Bassini, A., Jones, L.K., Chaplin, T., Linder, B., de Bruijn, D.R., Meese, E., Young, B.D. Blood (2002) [Pubmed]
  3. The synovial sarcoma associated protein SYT interacts with the acute leukemia associated protein AF10. de Bruijn, D.R., dos Santos, N.R., Thijssen, J., Balemans, M., Debernardi, S., Linder, B., Young, B.D., Geurts van Kessel, A. Oncogene (2001) [Pubmed]
  4. Acute monocytic leukemia with coexpression of minor BCR-ABL1 and PICALM-MLLT10 fusion genes along with overexpression of HOXA9. Sindt, A., Deau, B., Brahim, W., Staal, A., Visanica, S., Villarese, P., Rault, J.P., Macintyre, E., Delabesse, E. Genes Chromosomes Cancer (2006) [Pubmed]
  5. Alternative splicing in wild-type AF10 and CALM cDNAs and in AF10-CALM and CALM-AF10 fusion cDNAs produced by the t(10;11)(p13-14;q14-q21) suggests a potential role for truncated AF10 polypeptides. Silliman, C.C., McGavran, L., Wei, Q., Miller, L.A., Li, S., Hunger, S.P. Leukemia (1998) [Pubmed]
  6. Two unusual forms of human immunoglobulin E encoded by alternative RNA splicing of epsilon heavy chain membrane exons. Zhang, K., Saxon, A., Max, E.E. J. Exp. Med. (1992) [Pubmed]
  7. The t(10;11)(p13;q14) in the U937 cell line results in the fusion of the AF10 gene and CALM, encoding a new member of the AP-3 clathrin assembly protein family. Dreyling, M.H., Martinez-Climent, J.A., Zheng, M., Mao, J., Rowley, J.D., Bohlander, S.K. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  8. Molecular cytogenetic analysis of 10;11 rearrangements in acute myeloid leukemia. Van Limbergen, H., Poppe, B., Janssens, A., De Bock, R., De Paepe, A., Noens, L., Speleman, F. Leukemia (2002) [Pubmed]
  9. MLL and CALM are fused to AF10 in morphologically distinct subsets of acute leukemia with translocation t(10;11): both rearrangements are associated with a poor prognosis. Dreyling, M.H., Schrader, K., Fonatsch, C., Schlegelberger, B., Haase, D., Schoch, C., Ludwig, W., Löffler, H., Büchner, T., Wörmann, B., Hiddemann, W., Bohlander, S.K. Blood (1998) [Pubmed]
  10. Cytogenetic and molecular evidence of marrow involvement in extramedullary acute myeloid leukaemia. Lillington, D.M., Jaju, R.J., Shankar, A.G., Neat, M., Kearney, L., Young, B.D., Saha, V. Br. J. Haematol. (2000) [Pubmed]
  11. Dual-color split signal fluorescence in situ hybridization assays for the detection of CALM/AF10 in t(10;11)(p13;q14-q21)-positive acute leukemia. La Starza, R., Crescenzi, B., Krause, A., Pierini, V., Specchia, G., Bardi, A., Nieddu, R., Ariola, C., Nanni, M., Diverio, D., Aventin, A., Sborgia, M., Martelli, M.F., Bohlander, S.K., Mecucci, C. Haematologica (2006) [Pubmed]
  12. Differential effect of growth hormone and insulin-like growth factor-I, insulin-like growth factor-II, and insulin on Ig production and growth in human plasma cells. Kimata, H., Yoshida, A. Blood (1994) [Pubmed]
  13. The AF10 leucine zipper is required for leukemic transformation of myeloid progenitors by MLL-AF10. DiMartino, J.F., Ayton, P.M., Chen, E.H., Naftzger, C.C., Young, B.D., Cleary, M.L. Blood (2002) [Pubmed]
  14. The t(10;11) translocation in acute myeloid leukemia (M5) consistently fuses the leucine zipper motif of AF10 onto the HRX gene. Chaplin, T., Bernard, O., Beverloo, H.B., Saha, V., Hagemeijer, A., Berger, R., Young, B.D. Blood (1995) [Pubmed]
  15. The cloning, mapping and expression of a novel gene, BRL, related to the AF10 leukaemia gene. McCullagh, P., Chaplin, T., Meerabux, J., Grenzelias, D., Lillington, D., Poulsom, R., Gregorini, A., Saha, V., Young, B.D. Oncogene (1999) [Pubmed]
  16. The Drosophila homolog of human AF10/AF17 leukemia fusion genes (Dalf) encodes a zinc finger/leucine zipper nuclear protein required in the nervous system for maintaining EVE expression and normal growth. Bahri, S.M., Chia, W., Yang, X. Mech. Dev. (2001) [Pubmed]
  17. Retinoic acid-induced growth inhibition of a human myeloma cell line via down-regulation of IL-6 receptors. Sidell, N., Taga, T., Hirano, T., Kishimoto, T., Saxon, A. J. Immunol. (1991) [Pubmed]
  18. Gene BR140, which is related to AF10 and AF17, maps to chromosome band 3p25. Gregorini, A., Sahin, F.I., Lillington, D.M., Meerabux, J., Saha, V., McCullagh, P., Bocci, M., Menevse, S., Papa, S., Young, B.D. Genes Chromosomes Cancer (1996) [Pubmed]
  19. MLL-MLLT10 fusion gene in pediatric acute megakaryoblastic leukemia. Morerio, C., Rapella, A., Tassano, E., Rosanda, C., Panarello, C. Leuk. Res. (2005) [Pubmed]
  20. Breakpoint heterogeneity in t(10;11) translocation in AML-M4/M5 resulting in fusion of AF10 and MLL is resolved by fluorescent in situ hybridization analysis. Beverloo, H.B., Le Coniat, M., Wijsman, J., Lillington, D.M., Bernard, O., de Klein, A., van Wering, E., Welborn, J., Young, B.D., Hagemeijer, A. Cancer Res. (1995) [Pubmed]
  21. Biochemical analyses of the AF10 protein: the extended LAP/PHD-finger mediates oligomerisation. Linder, B., Newman, R., Jones, L.K., Debernardi, S., Young, B.D., Freemont, P., Verrijzer, C.P., Saha, V. J. Mol. Biol. (2000) [Pubmed]
  22. A novel class of zinc finger/leucine zipper genes identified from the molecular cloning of the t(10;11) translocation in acute leukemia. Chaplin, T., Ayton, P., Bernard, O.A., Saha, V., Della Valle, V., Hillion, J., Gregorini, A., Lillington, D., Berger, R., Young, B.D. Blood (1995) [Pubmed]
  23. A novel MLL-AF10 fusion mRNA variant in a patient with acute myeloid leukemia detected by a new asymmetric reverse transcription PCR method. Hjorth-Sørensen, B., Pallisgaard, N., Grönholm, M., Hokland, P., Clausen, N., Jørgensen, P. Leukemia (1997) [Pubmed]
  24. Consistent detection of CALM-AF10 chimaeric transcripts in haematological malignancies with t(10;11)(p13;q14) and identification of novel transcripts. Narita, M., Shimizu, K., Hayashi, Y., Taki, T., Taniwaki, M., Hosoda, F., Kobayashi, H., Nakamura, H., Sadamori, N., Ohnishi, H., Bessho, F., Yanagisawa, M., Ohki, M. Br. J. Haematol. (1999) [Pubmed]
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