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. 1996 May 14;93(10):4804–4809. doi: 10.1073/pnas.93.10.4804

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.

M H Dreyling 1, J A Martinez-Climent 1, M Zheng 1, J Mao 1, J D Rowley 1, S K Bohlander 1
PMCID: PMC39360  PMID: 8643484

Abstract

The translocation t(10;11)(p13;q14) is a recurring chromosomal abnormality that has been observed in patients with acute lymphoblastic leukemia as well as acute myeloid leukemia. We have recently reported that the monocytic cell line U937 has a t(10;11)(p13;q14) translocation. 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. AF10, a putative transcription factor, had recently been cloned as one of the fusion partners of MLL. CALM has a very high homology in its N-terminal third to the murine ap-3 gene which is one of the clathrin assembly proteins. The N-terminal region of ap-3 has been shown to bind to clathrin and to have a high-affinity binding site for phosphoinositols. 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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alkema M. J., Wiegant J., Raap A. K., Berns A., van Lohuizen M. Characterization and chromosomal localization of the human proto-oncogene BMI-1. Hum Mol Genet. 1993 Oct;2(10):1597–1603. doi: 10.1093/hmg/2.10.1597. [DOI] [PubMed] [Google Scholar]
  2. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
  3. Berger R., Le Coniat M., Derré J., Vecchione D., Chen S. J. Chromosomal rearrangement on chromosome 11q14-q21 in T cell acute lymphoblastic leukemia. Leukemia. 1989 Aug;3(8):560–562. [PubMed] [Google Scholar]
  4. Bernard O. A., Mauchauffe M., Mecucci C., Van den Berghe H., Berger R. A novel gene, AF-1p, fused to HRX in t(1;11)(p32;q23), is not related to AF-4, AF-9 nor ENL. Oncogene. 1994 Apr;9(4):1039–1045. [PubMed] [Google Scholar]
  5. 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. 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. Cancer Res. 1995 Oct 1;55(19):4220–4224. [PubMed] [Google Scholar]
  6. Bohlander S. K., Espinosa R., 3rd, Fernald A. A., Rowley J. D., Le Beau M. M., Díaz M. O. Sequence-independent amplification and labeling of yeast artificial chromosomes for fluorescence in situ hybridization. Cytogenet Cell Genet. 1994;65(1-2):108–110. doi: 10.1159/000133612. [DOI] [PubMed] [Google Scholar]
  7. Breen T. R., Harte P. J. Molecular characterization of the trithorax gene, a positive regulator of homeotic gene expression in Drosophila. Mech Dev. 1991 Sep;35(2):113–127. doi: 10.1016/0925-4773(91)90062-b. [DOI] [PubMed] [Google Scholar]
  8. Carter M., Kalwinsky D. K., Mirro J., Jr, Behm F. G., Head D., Huddleston T. F., Raimondi S. C. The t(10;11)(p14;q21) translocation in three children with acute myeloblastic leukemia. Leukemia. 1991 Jul;5(7):561–565. [PubMed] [Google Scholar]
  9. Chaplin T., Ayton P., Bernard O. A., Saha V., Della Valle V., Hillion J., Gregorini A., Lillington D., Berger R., Young B. D. A novel class of zinc finger/leucine zipper genes identified from the molecular cloning of the t(10;11) translocation in acute leukemia. Blood. 1995 Mar 15;85(6):1435–1441. [PubMed] [Google Scholar]
  10. Chaplin T., Bernard O., Beverloo H. B., Saha V., Hagemeijer A., Berger R., Young B. D. The t(10;11) translocation in acute myeloid leukemia (M5) consistently fuses the leucine zipper motif of AF10 onto the HRX gene. Blood. 1995 Sep 15;86(6):2073–2076. [PubMed] [Google Scholar]
  11. Cohen D., Chumakov I., Weissenbach J. A first-generation physical map of the human genome. Nature. 1993 Dec 16;366(6456):698–701. doi: 10.1038/366698a0. [DOI] [PubMed] [Google Scholar]
  12. Djabali M., Selleri L., Parry P., Bower M., Young B. D., Evans G. A. A trithorax-like gene is interrupted by chromosome 11q23 translocations in acute leukaemias. Nat Genet. 1992 Oct;2(2):113–118. doi: 10.1038/ng1092-113. [DOI] [PubMed] [Google Scholar]
  13. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  14. Fischkoff S. A., Testa J. R., Schiffer C. A. Acute eosinophilic leukemia with a (10;11) chromosomal translocation. Leukemia. 1988 Jun;2(6):394–397. [PubMed] [Google Scholar]
  15. Gu Y., Nakamura T., Alder H., Prasad R., Canaani O., Cimino G., Croce C. M., 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. 1992 Nov 13;71(4):701–708. doi: 10.1016/0092-8674(92)90603-a. [DOI] [PubMed] [Google Scholar]
  16. Haupt Y., Alexander W. S., Barri G., Klinken S. P., Adams J. M. Novel zinc finger gene implicated as myc collaborator by retrovirally accelerated lymphomagenesis in E mu-myc transgenic mice. Cell. 1991 May 31;65(5):753–763. doi: 10.1016/0092-8674(91)90383-a. [DOI] [PubMed] [Google Scholar]
  17. Heim S., Békàssy A. N., Garwicz S., Heldrup J., Kristoffersson U., Mandahl N., Wiebe T., Mitelman F. Bone marrow karyotypes in 94 children with acute leukemia. Eur J Haematol. 1990 Apr;44(4):227–233. doi: 10.1111/j.1600-0609.1990.tb00384.x. [DOI] [PubMed] [Google Scholar]
  18. Higgins D. G., Bleasby A. J., Fuchs R. CLUSTAL V: improved software for multiple sequence alignment. Comput Appl Biosci. 1992 Apr;8(2):189–191. doi: 10.1093/bioinformatics/8.2.189. [DOI] [PubMed] [Google Scholar]
  19. Kobayashi H., Thirman M. J., Rowley J. D. U937 cell line has a t(10;11)(p13-14;q14-21) rather than a deletion of 11q. Genes Chromosomes Cancer. 1995 Jul;13(3):217–218. doi: 10.1002/gcc.2870130312. [DOI] [PubMed] [Google Scholar]
  20. Le Beau M. M., Bitter M. A., Kaneko Y., Ueshima Y., Rowley J. D. Insertion (10;11)(p11;q23q24) in two cases of acute monocytic leukemia. Leuk Res. 1985;9(5):605–611. doi: 10.1016/0145-2126(85)90140-7. [DOI] [PubMed] [Google Scholar]
  21. Lindner R., Ungewickell E. Light-chain-independent binding of adaptors, AP180, and auxilin to clathrin. Biochemistry. 1991 Sep 17;30(37):9097–9101. doi: 10.1021/bi00101a027. [DOI] [PubMed] [Google Scholar]
  22. Morris S. A., Schröder S., Plessmann U., Weber K., Ungewickell E. Clathrin assembly protein AP180: primary structure, domain organization and identification of a clathrin binding site. EMBO J. 1993 Feb;12(2):667–675. doi: 10.1002/j.1460-2075.1993.tb05700.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Morrissey J., Tkachuk D. C., Milatovich A., Francke U., Link M., Cleary M. L. A serine/proline-rich protein is fused to HRX in t(4;11) acute leukemias. Blood. 1993 Mar 1;81(5):1124–1131. [PubMed] [Google Scholar]
  24. Murphy J. E., Keen J. H. Recognition sites for clathrin-associated proteins AP-2 and AP-3 on clathrin triskelia. J Biol Chem. 1992 May 25;267(15):10850–10855. [PubMed] [Google Scholar]
  25. Murphy J. E., Pleasure I. T., Puszkin S., Prasad K., Keen J. H. Clathrin assembly protein AP-3. The identity of the 155K protein, AP 180, and NP185 and demonstration of a clathrin binding domain. J Biol Chem. 1991 Mar 5;266(7):4401–4408. [PubMed] [Google Scholar]
  26. Nakamura T., Alder H., Gu Y., Prasad R., Canaani O., Kamada N., Gale R. P., Lange B., Crist W. M., Nowell P. C. Genes on chromosomes 4, 9, and 19 involved in 11q23 abnormalities in acute leukemia share sequence homology and/or common motifs. Proc Natl Acad Sci U S A. 1993 May 15;90(10):4631–4635. doi: 10.1073/pnas.90.10.4631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Norris F. A., Ungewickell E., Majerus P. W. Inositol hexakisphosphate binds to clathrin assembly protein 3 (AP-3/AP180) and inhibits clathrin cage assembly in vitro. J Biol Chem. 1995 Jan 6;270(1):214–217. doi: 10.1074/jbc.270.1.214. [DOI] [PubMed] [Google Scholar]
  28. Perry D. G., Li S., Hanson V., Puszkin S. Neuromuscular junctions contain NP185: the multifunctional protein is located at the presynaptic site. J Neurosci Res. 1992 Nov;33(3):408–417. doi: 10.1002/jnr.490330307. [DOI] [PubMed] [Google Scholar]
  29. Pley U., Parham P. Clathrin: its role in receptor-mediated vesicular transport and specialized functions in neurons. Crit Rev Biochem Mol Biol. 1993;28(5):431–464. doi: 10.3109/10409239309078441. [DOI] [PubMed] [Google Scholar]
  30. Prasad R., Gu Y., Alder H., Nakamura T., Canaani O., Saito H., Huebner K., Gale R. P., Nowell P. C., Kuriyama K. Cloning of the ALL-1 fusion partner, the AF-6 gene, involved in acute myeloid leukemias with the t(6;11) chromosome translocation. Cancer Res. 1993 Dec 1;53(23):5624–5628. [PubMed] [Google Scholar]
  31. Prasad R., Leshkowitz D., Gu Y., Alder H., Nakamura T., Saito H., Huebner K., Berger R., Croce C. M., Canaani E. Leucine-zipper dimerization motif encoded by the AF17 gene fused to ALL-1 (MLL) in acute leukemia. Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):8107–8111. doi: 10.1073/pnas.91.17.8107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Rabbitts T. H. Chromosomal translocations in human cancer. Nature. 1994 Nov 10;372(6502):143–149. doi: 10.1038/372143a0. [DOI] [PubMed] [Google Scholar]
  33. Ralph P., Harris P. E., Punjabi C. J., Welte K., Litcofsky P. B., Ho M. K., Rubin B. Y., Moore M. A., Springer T. A. Lymphokine inducing "terminal differentiation" of the human monoblast leukemia line U937: a role for gamma interferon. Blood. 1983 Dec;62(6):1169–1175. [PubMed] [Google Scholar]
  34. Ralph P., Moore M. A., Nilsson K. Lysozyme synthesis by established human and murine histiocytic lymphoma cell lines. J Exp Med. 1976 Jun 1;143(6):1528–1533. doi: 10.1084/jem.143.6.1528. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Rowley J. D., Diaz M. O., Espinosa R., 3rd, Patel Y. D., van Melle E., Ziemin S., Taillon-Miller P., Lichter P., Evans G. A., Kersey J. H. Mapping chromosome band 11q23 in human acute leukemia with biotinylated probes: identification of 11q23 translocation breakpoints with a yeast artificial chromosome. Proc Natl Acad Sci U S A. 1990 Dec;87(23):9358–9362. doi: 10.1073/pnas.87.23.9358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Sait S. N., Dal Cin P., Sandberg A. A. Recurrent involvement of 11q13 in acute nonlymphocytic leukemia. Cancer Genet Cytogenet. 1987 Jun;26(2):351–354. doi: 10.1016/0165-4608(87)90069-0. [DOI] [PubMed] [Google Scholar]
  37. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Shipley J. M., Sheppard D. M., Sheer D. Karyotypic analysis of the human monoblastic cell line U937. Cancer Genet Cytogenet. 1988 Feb;30(2):277–284. doi: 10.1016/0165-4608(88)90195-1. [DOI] [PubMed] [Google Scholar]
  39. Shipley J., Williams S., O'Byrne A., Kearney L., Jones T., Young B., Dyer M., Catovsky D., Sheer D., Gusterson B. Characterization of a t(10;11)(p13-14;q14-21) in the monoblastic cell line U937. Genes Chromosomes Cancer. 1995 Jun;13(2):138–142. doi: 10.1002/gcc.2870130211. [DOI] [PubMed] [Google Scholar]
  40. Sousa R., Tannery N. H., Zhou S., Lafer E. M. Characterization of a novel synapse-specific protein. I. Developmental expression and cellular localization of the F1-20 protein and mRNA. J Neurosci. 1992 Jun;12(6):2130–2143. doi: 10.1523/JNEUROSCI.12-06-02130.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Sundström C., Nilsson K. Establishment and characterization of a human histiocytic lymphoma cell line (U-937). Int J Cancer. 1976 May 15;17(5):565–577. doi: 10.1002/ijc.2910170504. [DOI] [PubMed] [Google Scholar]
  42. Thirman M. J., Gill H. J., Burnett R. C., Mbangkollo D., McCabe N. R., Kobayashi H., Ziemin-van der Poel S., Kaneko Y., Morgan R., Sandberg A. A. Rearrangement of the MLL gene in acute lymphoblastic and acute myeloid leukemias with 11q23 chromosomal translocations. N Engl J Med. 1993 Sep 23;329(13):909–914. doi: 10.1056/NEJM199309233291302. [DOI] [PubMed] [Google Scholar]
  43. Thirman M. J., Levitan D. A., Kobayashi H., Simon M. C., Rowley J. D. Cloning of ELL, a gene that fuses to MLL in a t(11;19)(q23;p13.1) in acute myeloid leukemia. Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12110–12114. doi: 10.1073/pnas.91.25.12110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Tkachuk D. C., Kohler S., Cleary M. L. Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias. Cell. 1992 Nov 13;71(4):691–700. doi: 10.1016/0092-8674(92)90602-9. [DOI] [PubMed] [Google Scholar]
  45. Ye W., Ali N., Bembenek M. E., Shears S. B., Lafer E. M. Inhibition of clathrin assembly by high affinity binding of specific inositol polyphosphates to the synapse-specific clathrin assembly protein AP-3. J Biol Chem. 1995 Jan 27;270(4):1564–1568. [PubMed] [Google Scholar]
  46. Ye W., Lafer E. M. Clathrin binding and assembly activities of expressed domains of the synapse-specific clathrin assembly protein AP-3. J Biol Chem. 1995 May 5;270(18):10933–10939. doi: 10.1074/jbc.270.18.10933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Zeleznik-Le N. J., Harden A. M., Rowley J. D. 11q23 translocations split the "AT-hook" cruciform DNA-binding region and the transcriptional repression domain from the activation domain of the mixed-lineage leukemia (MLL) gene. Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10610–10614. doi: 10.1073/pnas.91.22.10610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Zhou S., Sousa R., Tannery N. H., Lafer E. M. Characterization of a novel synapse-specific protein. II. cDNA cloning and sequence analysis of the F1-20 protein. J Neurosci. 1992 Jun;12(6):2144–2155. doi: 10.1523/JNEUROSCI.12-06-02144.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Ziemin-van der Poel S., McCabe N. R., Gill H. J., Espinosa R., 3rd, Patel Y., Harden A., Rubinelli P., Smith S. D., LeBeau M. M., Rowley J. D. Identification of a gene, MLL, that spans the breakpoint in 11q23 translocations associated with human leukemias. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10735–10739. doi: 10.1073/pnas.88.23.10735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. van Lohuizen M., Verbeek S., Scheijen B., Wientjens E., van der Gulden H., Berns A. Identification of cooperating oncogenes in E mu-myc transgenic mice by provirus tagging. Cell. 1991 May 31;65(5):737–752. doi: 10.1016/0092-8674(91)90382-9. [DOI] [PubMed] [Google Scholar]

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