Home LiteratureArticle Details
PMID: 10339604 Published · ppublish English Case Reports Journal Article Research Support, U.S. Gov't, P.H.S.

MSF (MLL septin-like fusion), a fusion partner gene of MLL, in a therapy-related acute myeloid leukemia with a t(11;17)(q23;q25).

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 96 ·No. 11 ·1999-05-25 ·Pages 6428-33

Osaka M, Rowley JD, Zeleznik-Le NJ

Abstract

MLL (ALL1, Htrx, HRX), which is located on chromosome band 11q23, frequently is rearranged in patients with therapy-related acute myeloid leukemia who previously were treated with DNA topoisomerase II inhibitors. In this study, we have identified a fusion partner of MLL in a 10-year-old female who developed therapy-related acute myeloid leukemia 17 months after treatment for Hodgkin's disease. Leukemia cells of this patient had a t(11;17)(q23;q25), which involved MLL as demonstrated by Southern blot analysis. The partner gene was cloned from cDNA of the leukemia cells by use of a combination of adapter reverse transcriptase-PCR, rapid amplification of 5' cDNA ends, and BLAST database analysis to identify expressed sequence tags. The full-length cDNA of 2.8 kb was found to be an additional member of the septin family, therefore it was named MSF (MLL septin-like fusion). Members of the septin family conserve the GTP binding domain, localize in the cytoplasm, and interact with cytoskeletal filaments. A major 4-kb transcript of MSF was expressed ubiquitously; a 1.7-kb transcript was found in most tissues. An additional 3-kb transcript was found only in hematopoietic tissues. By amplification with MLL exon 5 forward primer and reverse primers in MSF, the appropriately sized products were obtained. MSF is highly homologous to hCDCrel-1, which is a partner gene of MLL in leukemias with a t(11;22)(q23;q11.2). Further analysis of MSF may help to delineate the function of MLL partner genes in leukemia, particularly in therapy-related leukemia.

MeSH Terms
Acute Disease Amino Acid Sequence Animals Antineoplastic Combined Chemotherapy Protocols/adverse effects Base Sequence Child Chromosome Mapping Chromosomes, Human, Pair 11 Chromosomes, Human, Pair 17 Cyclophosphamide/administration & dosage DNA-Binding Proteins/genetics Drosophila/genetics Female GTP Phosphohydrolases GTP-Binding Proteins/chemistry,genetics Histone-Lysine N-Methyltransferase Hodgkin Disease/drug therapy Humans Leukemia, Myeloid/chemically induced,genetics Male Molecular Sequence Data Myeloid-Lymphoid Leukemia Protein Organ Specificity Prednisone/administration & dosage Procarbazine/administration & dosage Proto-Oncogenes Reverse Transcriptase Polymerase Chain Reaction Septins Sequence Alignment Sequence Homology, Amino Acid Transcription Factors Translocation, Genetic Vincristine/administration & dosage Zinc Fingers
Chemicals
DNA-Binding Proteins KMT2A protein, human Transcription Factors Myeloid-Lymphoid Leukemia Protein Procarbazine Vincristine Cyclophosphamide Histone-Lysine N-Methyltransferase GTP Phosphohydrolases GTP-Binding Proteins SEPTIN9 protein, human Septins Prednisone
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Osaka M
Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
Rowley J D
Zeleznik-Le N J
Supplementary Concepts
COPP protocol (Protocol)
References (59)
59 references, click to expand
  1. Rearrangements of the MLL gene in therapy-related acute myeloid leukemia in patients previously treated with agents targeting DNA-topoisomerase II.
    Blood. 1993 Dec 15;82(12):3705-11 PMID: 8260707
  2. MLL is fused to CBP, a histone acetyltransferase, in therapy-related acute myeloid leukemia with a t(11;16)(q23;p13.3).
    Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8732-7 PMID: 9238046
  3. 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):2073-6 PMID: 7662954
  4. Immortalization and leukemic transformation of a myelomonocytic precursor by retrovirally transduced HRX-ENL.
    EMBO J. 1997 Jul 16;16(14):4226-37 PMID: 9250666
  5. The protooncogene product, PEBP2beta/CBFbeta, is mainly located in the cytoplasm and has an affinity with cytoskeletal structures.
    Oncogene. 1997 Aug 7;15(6):677-83 PMID: 9264408
  6. Defects in yolk sac hematopoiesis in Mll-null embryos.
    Blood. 1997 Sep 1;90(5):1799-806 PMID: 9292512
  7. Chimeric MLL products with a Ras binding cytoplasmic protein AF6 involved in t(6;11) (q27;q23) leukemia localize in the nucleus.
    Oncogene. 1997 Oct 2;15(14):1681-7 PMID: 9349501
  8. AF6q21, a novel partner of the MLL gene in t(6;11)(q21;q23), defines a forkhead transcriptional factor subfamily.
    Blood. 1997 Nov 1;90(9):3714-9 PMID: 9345057
  9. t(11;22)(q23;q11.2) In acute myeloid leukemia of infant twins fuses MLL with hCDCrel, a cell division cycle gene in the genomic region of deletion in DiGeorge and velocardiofacial syndromes.
    Proc Natl Acad Sci U S A. 1998 May 26;95(11):6413-8 PMID: 9600980
  10. Structure and expression of the human septin gene HCDCREL-1.
    Gene. 1998 Jun 8;212(2):229-36 PMID: 9611266
  11. ABI-1, a human homolog to mouse Abl-interactor 1, fuses the MLL gene in acute myeloid leukemia with t(10;11)(p11.2;q23).
    Blood. 1998 Aug 15;92(4):1125-30 PMID: 9694699
  12. Secondary leukemias induced by topoisomerase-targeted drugs.
    Biochim Biophys Acta. 1998 Oct 1;1400(1-3):233-55 PMID: 9748598
  13. Localization of a novel septin protein, hCDCrel-1, in neurons of human brain.
    Neuroreport. 1998 Aug 24;9(12):2907-12 PMID: 9760144
  14. The leukemic protein core binding factor beta (CBFbeta)-smooth-muscle myosin heavy chain sequesters CBFalpha2 into cytoskeletal filaments and aggregates.
    Mol Cell Biol. 1998 Dec;18(12):7432-43 PMID: 9819429
  15. Molecular basis of 11q23 rearrangements in hematopoietic malignant proliferations.
    Genes Chromosomes Cancer. 1995 Jun;13(2):75-85 PMID: 7542910
  16. Genetic control of the cell division cycle in yeast. IV. Genes controlling bud emergence and cytokinesis.
    Exp Cell Res. 1971 Dec;69(2):265-76 PMID: 4950437
  17. Immunofluorescence localization of the Saccharomyces cerevisiae CDC12 gene product to the vicinity of the 10-nm filaments in the mother-bud neck.
    Mol Cell Biol. 1987 Oct;7(10):3678-87 PMID: 3316985
  18. Basic local alignment search tool.
    J Mol Biol. 1990 Oct 5;215(3):403-10 PMID: 2231712
  19. Cellular morphogenesis in the Saccharomyces cerevisiae cell cycle: localization of the CDC3 gene product and the timing of events at the budding site.
    J Cell Biol. 1991 Feb;112(4):535-44 PMID: 1993729
  20. Complementary DNA sequencing: expressed sequence tags and human genome project.
    Science. 1991 Jun 21;252(5013):1651-6 PMID: 2047873
  21. Cellular morphogenesis in the Saccharomyces cerevisiae cell cycle: localization of the CDC11 gene product and the timing of events at the budding site.
    Dev Genet. 1991;12(4):281-92 PMID: 1934633
  22. 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):10735-9 PMID: 1720549
  23. Cloning of ALL-1, the locus involved in leukemias with the t(4;11)(q21;q23), t(9;11)(p22;q23), and t(11;19)(q23;p13) chromosome translocations.
    Cancer Res. 1991 Dec 15;51(24):6712-4 PMID: 1835902
  24. Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias.
    Cell. 1992 Nov 13;71(4):691-700 PMID: 1423624
  25. 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):701-8 PMID: 1423625
  26. A trithorax-like gene is interrupted by chromosome 11q23 translocations in acute leukaemias.
    Nat Genet. 1992 Oct;2(2):113-8 PMID: 1303259
  27. 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):4631-5 PMID: 8506309
  28. HRX involvement in de novo and secondary leukemias with diverse chromosome 11q23 abnormalities.
    Blood. 1993 Jun 15;81(12):3197-203 PMID: 8389614
  29. Components required for cytokinesis are important for bud site selection in yeast.
    J Cell Biol. 1993 Jul;122(2):373-86 PMID: 8320260
  30. 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):909-14 PMID: 8361504
  31. 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):5624-8 PMID: 8242616
  32. 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):1039-45 PMID: 8134107
  33. Rearrangements involving chromosome band 11Q23 in acute leukaemia.
    Semin Cancer Biol. 1993 Dec;4(6):377-85 PMID: 8142623
  34. The balanced and the unbalanced chromosome aberrations of acute myeloid leukemia may develop in different ways and may contribute differently to malignant transformation.
    Blood. 1994 May 15;83(10):2780-6 PMID: 8180374
  35. The Drosophila peanut gene is required for cytokinesis and encodes a protein similar to yeast putative bud neck filament proteins.
    Cell. 1994 May 6;77(3):371-9 PMID: 8181057
  36. Molecular cloning of a novel human cDNA homologous to CDC10 in Saccharomyces cerevisiae.
    Biochem Biophys Res Commun. 1994 Jul 15;202(1):82-7 PMID: 8037772
  37. 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):8107-11 PMID: 8058765
  38. ENL, the gene fused with HRX in t(11;19) leukemias, encodes a nuclear protein with transcriptional activation potential in lymphoid and myeloid cells.
    Blood. 1994 Sep 15;84(6):1747-52 PMID: 8080983
  39. 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):12110-4 PMID: 7991593
  40. Cloning and characterization of the t(X;11) breakpoint from a leukemic cell line identify a new member of the forkhead gene family.
    Genes Chromosomes Cancer. 1994 Oct;11(2):79-84 PMID: 7529552
  41. A novel gene, AF1q, fused to MLL in t(1;11) (q21;q23), is specifically expressed in leukemic and immature hematopoietic cells.
    Blood. 1995 Feb 1;85(3):650-6 PMID: 7833468
  42. Subcellular localization of the alpha and beta subunits of the acute myeloid leukemia-linked transcription factor PEBP2/CBF.
    Mol Cell Biol. 1995 Mar;15(3):1651-61 PMID: 7862156
  43. 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):1435-41 PMID: 7888665
  44. Chromosome band 11q23 translocation breakpoints are DNA topoisomerase II cleavage sites.
    Cancer Res. 1995 Oct 1;55(19):4287-92 PMID: 7671237
  45. Altered Hox expression and segmental identity in Mll-mutant mice.
    Nature. 1995 Nov 30;378(6556):505-8 PMID: 7477409
  46. Identification of AF-6 and canoe as putative targets for Ras.
    J Biol Chem. 1996 Jan 12;271(2):607-10 PMID: 8557659
  47. The secondary leukemias: challenges and research directions.
    J Natl Cancer Inst. 1996 Apr 3;88(7):407-18 PMID: 8618232
  48. Double knockout of the ALL-1 gene blocks hematopoietic differentiation in vitro.
    Cancer Res. 1996 Mar 15;56(6):1179-83 PMID: 8640793
  49. Core binding factor beta-smooth muscle myosin heavy chain chimeric protein involved in acute myeloid leukemia forms unusual nuclear rod-like structures in transformed NIH 3T3 cells.
    Proc Natl Acad Sci U S A. 1996 Feb 20;93(4):1630-5 PMID: 8643682
  50. Distribution of 11q23 breakpoints within the MLL breakpoint cluster region in de novo acute leukemia and in treatment-related acute myeloid leukemia: correlation with scaffold attachment regions and topoisomerase II consensus binding sites.
    Blood. 1996 Mar 1;87(5):1912-22 PMID: 8634439
  51. A purified Drosophila septin complex forms filaments and exhibits GTPase activity.
    J Cell Biol. 1996 May;133(3):605-16 PMID: 8636235
  52. An Mll-AF9 fusion gene made by homologous recombination causes acute leukemia in chimeric mice: a method to create fusion oncogenes.
    Cell. 1996 Jun 14;85(6):853-61 PMID: 8681380
  53. Alternative expression of platelet glycoprotein Ib(beta) mRNA from an adjacent 5' gene with an imperfect polyadenylation signal sequence.
    J Clin Invest. 1997 Feb 1;99(3):520-5 PMID: 9022087
  54. EEN encodes for a member of a new family of proteins containing an Src homology 3 domain and is the third gene located on chromosome 19p13 that fuses to MLL in human leukemia.
    Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2563-8 PMID: 9122235
  55. Disruption of a homolog of trithorax by 11q23 translocations: leukemogenic and transcriptional implications.
    Curr Top Microbiol Immunol. 1997;220:1-23 PMID: 9103672
  56. A breakpoint map of recurrent chromosomal rearrangements in human neoplasia.
    Nat Genet. 1997 Apr;15 Spec No:417-74 PMID: 9140409
  57. The t(11;16)(q23;p13) translocation in myelodysplastic syndrome fuses the MLL gene to the CBP gene.
    Blood. 1997 Jun 1;89(11):3945-50 PMID: 9166831
  58. Nedd5, a mammalian septin, is a novel cytoskeletal component interacting with actin-based structures.
    Genes Dev. 1997 Jun 15;11(12):1535-47 PMID: 9203580
  59. Molecular analysis of 13 cases of MLL/11q23 secondary acute leukemia and identification of topoisomerase II consensus-binding sequences near the chromosomal breakpoint of a secondary leukemia with the t(4;11).
    Leukemia. 1995 Aug;9(8):1305-12 PMID: 7643617
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.96.11.6428
Published
1999-05-25
Pages
6428-33
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC26898
Subset
IM
Grants
NCI NIH HHS · P01 CA040046 · United States
NCI NIH HHS · CA42557 · United States
NCI NIH HHS · P01 CA40046 · United States
Databases
GENBANK
AF123052
External Links
PubMed source DOI: 10.1073/pnas.96.11.6428 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2