DOI: 10.1182/blood-2005-08-3498. A murine Mll-AF4 knock-in model results in lymphoid and myeloid deregulation and hematologic malignancy

A murine Mll-AF4 knock-in model results in lymphoid and myeloid deregulation and hematologic malignancy

10.1182/blood-2005-08-3498

Crossref journal-article

American Society of Hematology

Blood (234)

Abstract

The 2 most frequent human MLL hematopoietic malignancies involve either AF4 or AF9 as fusion partners; each has distinct biology but the role of the fusion partner is not clear. We produced Mll-AF4 knock-in (KI) mice by homologous recombination in embryonic stem cells and compared them with Mll-AF9 KI mice. Young Mll-AF4 mice had lymphoid and myeloid deregulation manifest by increased lymphoid and myeloid cells in hematopoietic organs. In vitro, bone marrow cells from young mice formed unique mixed pro-B lymphoid (B220+CD19+CD43+sIgM–, PAX5+, TdT+, IgH rearranged)/myeloid (CD11b/Mac1+, c-fms+, lysozyme+) colonies when grown in IL-7– and Flt3 ligand-containing media. Mixed lymphoid/myeloid hyperplasia and hematologic malignancies (most frequently B-cell lymphomas) developed in Mll-AF4 mice after prolonged latency; long latency to malignancy indicates that Mll-AF4–induced lymphoid/myeloid deregulation alone is insufficient to produce malignancy. In contrast, young Mll-AF9 mice had predominately myeloid deregulation in vivo and in vitro and developed myeloid malignancies. The early onset of distinct mixed lymphoid/myeloid lineage deregulation in Mll-AF4 mice shows evidence for both “instructive” and “noninstructive” roles for AF4 and AF9 as partners in MLL fusion genes. The molecular basis for “instruction” and secondary cooperating mutations can now be studied in our Mll-AF4 model.

Bibliography

Chen, W., Li, Q., Hudson, W. A., Kumar, A., Kirchhof, N., & Kersey, J. H. (2006). A murine Mll-AF4 knock-in model results in lymphoid and myeloid deregulation and hematologic malignancy. Blood, 108(2), 669â677.

Authors 6

Weili Chen (first)
Quanzhi Li (additional)
Wendy A. Hudson (additional)
Ashish Kumar (additional)
Nicole Kirchhof (additional)
John H. Kersey (additional)

References 52 Referenced 107

Dates

Type	When
Created	19 years, 5 months ago (March 21, 2006, 9:54 p.m.)
Deposited	2 years, 3 months ago (May 6, 2023, 4:51 p.m.)
Indexed	3 days, 14 hours ago (Aug. 31, 2025, 6:16 a.m.)
Issued	19 years, 1 month ago (July 15, 2006)
Published	19 years, 1 month ago (July 15, 2006)
Published Print	19 years, 1 month ago (July 15, 2006)

Funders 0

None

BibTeX

@article{Chen_2006, title={A murine Mll-AF4 knock-in model results in lymphoid and myeloid deregulation and hematologic malignancy}, volume={108}, ISSN={1528-0020}, url={http://dx.doi.org/10.1182/blood-2005-08-3498}, DOI={10.1182/blood-2005-08-3498}, number={2}, journal={Blood}, publisher={American Society of Hematology}, author={Chen, Weili and Li, Quanzhi and Hudson, Wendy A. and Kumar, Ashish and Kirchhof, Nicole and Kersey, John H.}, year={2006}, month=jul, pages={669–677} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        31
      ]
    ],
    "date-time": "2025-08-31T10:16:09Z",
    "timestamp": 1756635369078
  },
  "reference-count": 52,
  "publisher": "American Society of Hematology",
  "issue": "2",
  "content-domain": {
    "domain": [
      "ashpublications.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2006,
        7,
        15
      ]
    ]
  },
  "abstract": "<jats:p>The 2 most frequent human MLL hematopoietic malignancies involve either AF4 or AF9 as fusion partners; each has distinct biology but the role of the fusion partner is not clear. We produced Mll-AF4 knock-in (KI) mice by homologous recombination in embryonic stem cells and compared them with Mll-AF9 KI mice. Young Mll-AF4 mice had lymphoid and myeloid deregulation manifest by increased lymphoid and myeloid cells in hematopoietic organs. In vitro, bone marrow cells from young mice formed unique mixed pro-B lymphoid (B220+CD19+CD43+sIgM\u2013, PAX5+, TdT+, IgH rearranged)/myeloid (CD11b/Mac1+, c-fms+, lysozyme+) colonies when grown in IL-7\u2013 and Flt3 ligand-containing media. Mixed lymphoid/myeloid hyperplasia and hematologic malignancies (most frequently B-cell lymphomas) developed in Mll-AF4 mice after prolonged latency; long latency to malignancy indicates that Mll-AF4\u2013induced lymphoid/myeloid deregulation alone is insufficient to produce malignancy. In contrast, young Mll-AF9 mice had predominately myeloid deregulation in vivo and in vitro and developed myeloid malignancies. The early onset of distinct mixed lymphoid/myeloid lineage deregulation in Mll-AF4 mice shows evidence for both \u201cinstructive\u201d and \u201cnoninstructive\u201d roles for AF4 and AF9 as partners in MLL fusion genes. The molecular basis for \u201cinstruction\u201d and secondary cooperating mutations can now be studied in our Mll-AF4 model.</jats:p>",
  "DOI": "10.1182/blood-2005-08-3498",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2006,
        3,
        22
      ]
    ],
    "date-time": "2006-03-22T02:54:02Z",
    "timestamp": 1142996042000
  },
  "page": "669-677",
  "update-policy": "http://dx.doi.org/10.1182/blood.2019cm0000",
  "source": "Crossref",
  "is-referenced-by-count": 107,
  "title": "A murine Mll-AF4 knock-in model results in lymphoid and myeloid deregulation and hematologic malignancy",
  "prefix": "10.1182",
  "volume": "108",
  "author": [
    {
      "given": "Weili",
      "family": "Chen",
      "sequence": "first",
      "affiliation": [
        {
          "name": "From the Cancer Center, University of Minnesota, Minneapolis; Department of Pediatrics, University of Minnesota, Minneapolis; Veterinary Diagnostic Lab & Cancer Center Histopathology, University of Minnesota, St Paul; and Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis."
        }
      ]
    },
    {
      "given": "Quanzhi",
      "family": "Li",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "From the Cancer Center, University of Minnesota, Minneapolis; Department of Pediatrics, University of Minnesota, Minneapolis; Veterinary Diagnostic Lab & Cancer Center Histopathology, University of Minnesota, St Paul; and Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis."
        }
      ]
    },
    {
      "given": "Wendy A.",
      "family": "Hudson",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "From the Cancer Center, University of Minnesota, Minneapolis; Department of Pediatrics, University of Minnesota, Minneapolis; Veterinary Diagnostic Lab & Cancer Center Histopathology, University of Minnesota, St Paul; and Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis."
        }
      ]
    },
    {
      "given": "Ashish",
      "family": "Kumar",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "From the Cancer Center, University of Minnesota, Minneapolis; Department of Pediatrics, University of Minnesota, Minneapolis; Veterinary Diagnostic Lab & Cancer Center Histopathology, University of Minnesota, St Paul; and Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis."
        }
      ]
    },
    {
      "given": "Nicole",
      "family": "Kirchhof",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "From the Cancer Center, University of Minnesota, Minneapolis; Department of Pediatrics, University of Minnesota, Minneapolis; Veterinary Diagnostic Lab & Cancer Center Histopathology, University of Minnesota, St Paul; and Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis."
        }
      ]
    },
    {
      "given": "John H.",
      "family": "Kersey",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "From the Cancer Center, University of Minnesota, Minneapolis; Department of Pediatrics, University of Minnesota, Minneapolis; Veterinary Diagnostic Lab & Cancer Center Histopathology, University of Minnesota, St Paul; and Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis."
        }
      ]
    }
  ],
  "member": "234",
  "reference": [
    {
      "key": "2019111905054328500_REF1",
      "doi-asserted-by": "crossref",
      "unstructured": "Ziemin-van der Poel S, McCabe NR, Gill HJ, et al. Identification of a gene, MLL, that spans the breakpoint in 11q23 translocations associated with human leukemias. Proc Natl Acad Sci U S A.1991;88: 10735-10739.",
      "DOI": "10.1073/pnas.88.23.10735"
    },
    {
      "key": "2019111905054328500_REF2",
      "doi-asserted-by": "crossref",
      "unstructured": "Ayton PM, Cleary ML. Molecular mechanisms of leukemogenesis mediated by MLL fusion proteins. Oncogene.2001;20: 5695-5707.",
      "DOI": "10.1038/sj.onc.1204639"
    },
    {
      "key": "2019111905054328500_REF3",
      "doi-asserted-by": "crossref",
      "unstructured": "Armstrong SA, Staunton JE, Silverman LB, et al. MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia. Nat Genet.2002;30: 41-47.",
      "DOI": "10.1038/ng765"
    },
    {
      "key": "2019111905054328500_REF4",
      "doi-asserted-by": "crossref",
      "unstructured": "Chen CS, Sorensen PH, Domer PH, et al. Molecular rearrangements on chromosome 11q23 predominate in infant acute lymphoblastic leukemia and are associated with specific biologic variables and poor outcome. Blood.1993;81: 2386-2393.",
      "DOI": "10.1182/blood.V81.9.2386.2386"
    },
    {
      "key": "2019111905054328500_REF5",
      "doi-asserted-by": "crossref",
      "unstructured": "Dimartino JF, Cleary ML. Mll rearrangements in haematological malignancies: lessons from clinical and biological studies. Br J Haematol.1999;106: 614-626.",
      "DOI": "10.1046/j.1365-2141.1999.01439.x"
    },
    {
      "key": "2019111905054328500_REF6",
      "doi-asserted-by": "crossref",
      "unstructured": "Hiwatari M, Taki T, Taketani T, et al. Fusion of an AF4-related gene, LAF4, to MLL in childhood acute lymphoblastic leukemia with t(2;11)(q11; q23). Oncogene.2003;22: 2851-2855.",
      "DOI": "10.1038/sj.onc.1206389"
    },
    {
      "key": "2019111905054328500_",
      "doi-asserted-by": "crossref",
      "unstructured": "Rubnitz JE, Link MP, Shuster JJ, et al. Frequency and prognostic significance of HRX rearrangements in infant acute lymphoblastic leukemia: a Pediatric Oncology Group study. Blood.1994;84: 570-573.",
      "DOI": "10.1182/blood.V84.2.570.570"
    },
    {
      "key": "2019111905054328500_REF8",
      "doi-asserted-by": "crossref",
      "unstructured": "Secker-Walker LM. General Report on the European Union Concerted Action Workshop on 11q23, London, UK, May 1997. Leukemia.1998;12: 776-778.",
      "DOI": "10.1038/sj.leu.2401011"
    },
    {
      "key": "2019111905054328500_",
      "doi-asserted-by": "crossref",
      "unstructured": "Stong RC, Korsmeyer SJ, Parkin JL, Arthur DC, Kersey JH. Human acute leukemia cell line with the t(4;11) chromosomal rearrangement exhibits B lineage and monocytic characteristics. Blood.1985;65: 21-31.",
      "DOI": "10.1182/blood.V65.1.21.21"
    },
    {
      "key": "2019111905054328500_REF10",
      "doi-asserted-by": "crossref",
      "unstructured": "Taki T, Kano H, Taniwaki M, Sako M, Yanagisawa M, Hayashi Y. AF5q31, a newly identified AF4-related gene, is fused to MLL in infant acute lymphoblastic leukemia with ins(5;11)(q31;q13q23). Proc Natl Acad Sci U S A.1999;96: 14535-14540.",
      "DOI": "10.1073/pnas.96.25.14535"
    },
    {
      "key": "2019111905054328500_REF11",
      "doi-asserted-by": "crossref",
      "unstructured": "Corral J, Lavenir I, Impey H, et al. An Mll-AF9 fusion gene made by homologous recombination causes acute leukemia in chimeric mice: a method to create fusion oncogenes. Cell.1996;85: 853-861.",
      "DOI": "10.1016/S0092-8674(00)81269-6"
    },
    {
      "key": "2019111905054328500_REF12",
      "doi-asserted-by": "crossref",
      "unstructured": "Daser A, Rabbitts TH. The versatile mixed lineage leukaemia gene MLL and its many associations in leukaemogenesis. Semin Cancer Biol.2005;15: 175-188.",
      "DOI": "10.1016/j.semcancer.2005.01.007"
    },
    {
      "key": "2019111905054328500_REF13",
      "doi-asserted-by": "crossref",
      "unstructured": "Muyrers-Chen I, Rozovskaia T, Lee N, et al. Expression of leukemic MLL fusion proteins in Drosophila affects cell cycle control and chromosome morphology. Oncogene.2004;23: 8639-8648.",
      "DOI": "10.1038/sj.onc.1207904"
    },
    {
      "key": "2019111905054328500_REF14",
      "doi-asserted-by": "crossref",
      "unstructured": "Caslini C, Serna A, Rossi V, Introna M, Biondi A. Modulation of cell cycle by graded expression of MLL-AF4 fusion oncoprotein. Leukemia.2004;18: 1064-1071.",
      "DOI": "10.1038/sj.leu.2403321"
    },
    {
      "key": "2019111905054328500_REF15",
      "doi-asserted-by": "crossref",
      "unstructured": "Domer PH, Fakharzadeh SS, Chen CS, et al. Acute mixed-lineage leukemia t(4;11)(q21;q23) generates an MLL-AF4 fusion product. Proc Natl Acad Sci U S A.1993;90: 7884-7888.",
      "DOI": "10.1073/pnas.90.16.7884"
    },
    {
      "key": "2019111905054328500_REF16",
      "unstructured": "Hilden JM, Chen CS, Moore R, Frestedt J, Kersey JH. Heterogeneity in MLL/AF-4 fusion messenger RNA detected by the polymerase chain reaction in t(4;11) acute leukemia. Cancer Res.1993;53: 3853-3856."
    },
    {
      "key": "2019111905054328500_REF17",
      "doi-asserted-by": "crossref",
      "unstructured": "Kumar AR, Hudson WA, Chen W, Nishiuchi R, Yao Q, Kersey JH. Hoxa9 influences the phenotype but not the incidence of Mll-AF9 fusion gene leukemia. Blood.2004;103: 1823-1828.",
      "DOI": "10.1182/blood-2003-07-2582"
    },
    {
      "key": "2019111905054328500_REF18",
      "doi-asserted-by": "crossref",
      "unstructured": "Bowman EP, Campbell JJ, Soler D, et al. Developmental switches in chemokine response profiles during B cell differentiation and maturation. J Exp Med.2000;191: 1303-1318.",
      "DOI": "10.1084/jem.191.8.1303"
    },
    {
      "key": "2019111905054328500_REF19",
      "unstructured": "The Gene Quantification Web pages. REST (Relative Expression Software Tool). http://www.qpcr-applications.com. Accessed December 20, 2005."
    },
    {
      "key": "2019111905054328500_REF20",
      "doi-asserted-by": "crossref",
      "unstructured": "Zeisig BB, Milne T, Garcia-Cuellar MP, et al. Hoxa9 and Meis1 are key targets for MLL-ENL-mediated cellular immortalization. Mol Cell Biol.2004;24: 617-628.",
      "DOI": "10.1128/MCB.24.2.617-628.2004"
    },
    {
      "key": "2019111905054328500_REF21",
      "doi-asserted-by": "crossref",
      "unstructured": "Kurosawa Y, Bohmer HV, Haaa W, Sakano H, Trauneker A, Tonegawa S. Identification of D segments of immunoglobulin heavy-chain gene and their rearrangement in T lymphocytes. Nature.1981;290: 565-571.",
      "DOI": "10.1038/290565a0"
    },
    {
      "key": "2019111905054328500_REF22",
      "doi-asserted-by": "crossref",
      "unstructured": "Li Q, Frestedt JL, Kersey JH. AF4 encodes a ubiquitous protein that in both native and MLL-AF4 fusion types localizes to subnuclear compartments. Blood.1998;92: 3841-3847.",
      "DOI": "10.1182/blood.V92.10.3841"
    },
    {
      "key": "2019111905054328500_REF23",
      "doi-asserted-by": "crossref",
      "unstructured": "Hunte BE, Hudak S, Campbell D, Xu Y, Rennick D. flk2/flt3 ligand is a potent cofactor for the growth of primitive B cell progenitors. J Immunol.1996;156: 489-496.",
      "DOI": "10.4049/jimmunol.156.2.489"
    },
    {
      "key": "2019111905054328500_REF24",
      "doi-asserted-by": "crossref",
      "unstructured": "So CW, Karsunky H, Passegue E, Cozzio A, Weissman IL, Cleary ML. MLL-GAS7 transforms multipotent hematopoietic progenitors and induces mixed lineage leukemias in mice. Cancer Cell.2003;3: 161-171.",
      "DOI": "10.1016/S1535-6108(03)00019-9"
    },
    {
      "key": "2019111905054328500_REF25",
      "doi-asserted-by": "crossref",
      "unstructured": "Johnson JJ, Chen W, Hudson W, et al. Prenatal and postnatal myeloid cells demonstrate stepwise progression in the pathogenesis of MLL fusion gene leukemia. Blood.2003;101: 3229-3235.",
      "DOI": "10.1182/blood-2002-05-1515"
    },
    {
      "key": "2019111905054328500_REF26",
      "doi-asserted-by": "crossref",
      "unstructured": "Lavau C, Szilvassy SJ, Slany R, Cleary ML. Immortalization and leukemic transformation of a myelomonocytic precursor by retrovirally transduced HRX-ENL. EMBO J.1997;16: 4226-4237.",
      "DOI": "10.1093/emboj/16.14.4226"
    },
    {
      "key": "2019111905054328500_REF27",
      "doi-asserted-by": "crossref",
      "unstructured": "Morse HC 3rd, Anver MR, Fredrickson TN, et al. Bethesda proposals for classification of lymphoid neoplasms in mice. Blood.2002;100: 246-258.",
      "DOI": "10.1182/blood.V100.1.246"
    },
    {
      "key": "2019111905054328500_REF28",
      "doi-asserted-by": "crossref",
      "unstructured": "Cattoretti G, Pasqualucci L, Ballon G, et al. Deregulated BCL6 expression recapitulates the pathogenesis of human diffuse large B cell lymphomas in mice. Cancer Cell.2005;7: 445-455.",
      "DOI": "10.1016/j.ccr.2005.03.037"
    },
    {
      "key": "2019111905054328500_REF29",
      "doi-asserted-by": "crossref",
      "unstructured": "Kogan SC, Ward JM, Anver MR, et al. Bethesda proposals for classification of nonlymphoid hematopoietic neoplasms in mice. Blood.2002;100: 238-245.",
      "DOI": "10.1182/blood.V100.1.238"
    },
    {
      "key": "2019111905054328500_REF30",
      "doi-asserted-by": "crossref",
      "unstructured": "Dobson CL, Warren AJ, Pannell R, et al. The mll-AF9 gene fusion in mice controls myeloproliferation and specifies acute myeloid leukaemogenesis. EMBO J.1999;18: 3564-3574.",
      "DOI": "10.1093/emboj/18.13.3564"
    },
    {
      "key": "2019111905054328500_REF31",
      "doi-asserted-by": "crossref",
      "unstructured": "Yu BD, Hess JL, Horning SE, Brown GA, Korsmeyer SJ. Altered Hox expression and segmental identity in Mll-mutant mice. Nature.1995;378: 505-508.",
      "DOI": "10.1038/378505a0"
    },
    {
      "key": "2019111905054328500_REF32",
      "doi-asserted-by": "crossref",
      "unstructured": "Yu BD, Hanson RD, Hess JL, Horning SE, Korsmeyer SJ. MLL, a mammalian trithorax-group gene, functions as a transcriptional maintenance factor in morphogenesis. Proc Natl Acad Sci U S A.1998;95: 10632-10636.",
      "DOI": "10.1073/pnas.95.18.10632"
    },
    {
      "key": "2019111905054328500_REF33",
      "doi-asserted-by": "crossref",
      "unstructured": "Isaacs AM, Oliver PL, Jones EL, et al. A mutation in Af4 is predicted to cause cerebellar ataxia and cataracts in the robotic mouse. J Neurosci.2003;23: 1631-1637.",
      "DOI": "10.1523/JNEUROSCI.23-05-01631.2003"
    },
    {
      "key": "2019111905054328500_REF34",
      "doi-asserted-by": "crossref",
      "unstructured": "Isnard P, Core N, Naquet P, Djabali M. Altered lymphoid development in mice deficient for the mAF4 proto-oncogene. Blood.2000;96: 705-710.",
      "DOI": "10.1182/blood.V96.2.705"
    },
    {
      "key": "2019111905054328500_REF35",
      "doi-asserted-by": "crossref",
      "unstructured": "Ma C, Staudt LM. LAF-4 encodes a lymphoid nuclear protein with transactivation potential that is homologous to AF-4, the gene fused to MLL in t(4;11) leukemias. Blood.1996;87: 734-745.",
      "DOI": "10.1182/blood.V87.2.734.bloodjournal872734"
    },
    {
      "key": "2019111905054328500_REF36",
      "doi-asserted-by": "crossref",
      "unstructured": "Biondi A, Cimino G, Pieters R, Pui CH. Biological and therapeutic aspects of infant leukemia. Blood.2000;96: 24-33.",
      "DOI": "10.1182/blood.V96.1.24"
    },
    {
      "key": "2019111905054328500_REF37",
      "doi-asserted-by": "crossref",
      "unstructured": "Morrison SJ, Wandycz AM, Hemmati HD, Wright DE, Weissman IL. Identification of a lineage of multipotent hematopoietic progenitors. Development.1997;124: 1929-1939.",
      "DOI": "10.1242/dev.124.10.1929"
    },
    {
      "key": "2019111905054328500_REF38",
      "doi-asserted-by": "crossref",
      "unstructured": "Kersey JH, Wang D, Oberto M. Resistance of t(4;11) (MLL-AF4 fusion gene) leukemias to stress-induced cell death: possible mechanism for extensive extramedullary accumulation of cells and poor prognosis. Leukemia.1998;12: 1561-1564.",
      "DOI": "10.1038/sj.leu.2401148"
    },
    {
      "key": "2019111905054328500_REF39",
      "doi-asserted-by": "crossref",
      "unstructured": "Corapcioglu F, Olgun N, Sarrialioglu F, Uysal KM, Oren H, Sercan O. MLL-AF4 gene rearrangement in a child with Epstein-Barr virus-related post-transplant B-cell lymphoma. J Pediatr Hematol Oncol.2003;25: 740-742.",
      "DOI": "10.1097/00043426-200309000-00013"
    },
    {
      "key": "2019111905054328500_REF40",
      "doi-asserted-by": "crossref",
      "unstructured": "Cozzio A, Passegue E, Ayton PM, Karsunky H, Cleary ML, Weissman IL. Similar MLL-associated leukemias arising from self-renewing stem cells and short-lived myeloid progenitors. Genes Dev.2003;17: 3029-3035.",
      "DOI": "10.1101/gad.1143403"
    },
    {
      "key": "2019111905054328500_REF41",
      "doi-asserted-by": "crossref",
      "unstructured": "Wang J, Iwasaki H, Krivtsov A, et al. Conditional MLL-CBP targets GMP and models therapy-related myeloproliferative disease. EMBO J.2005;24: 368-381.",
      "DOI": "10.1038/sj.emboj.7600521"
    },
    {
      "key": "2019111905054328500_REF42",
      "unstructured": "Yao Q, Nishiuchi R, Li Q, Kumar AR, Hudson WA, Kersey JH. FLT3 expressing leukemias are selectively sensitive to inhibitors of the molecular chaperone heat shock protein 90 through destabilization of signal transduction-associated kinases. Clin Cancer Res.2003;9: 4483-4493."
    },
    {
      "key": "2019111905054328500_REF43",
      "doi-asserted-by": "crossref",
      "unstructured": "Ernst P, Wang J, Korsmeyer SJ. The role of MLL in hematopoiesis and leukemia. Curr Opin Hematol.2002;9: 282-287.",
      "DOI": "10.1097/00062752-200207000-00004"
    },
    {
      "key": "2019111905054328500_REF44",
      "doi-asserted-by": "crossref",
      "unstructured": "Castelli-Gair J, Greig S, Micklem G, Akam M. Dissecting the temporal requirements for homeotic gene function. Development.1994;120: 1983-1995.",
      "DOI": "10.1242/dev.120.7.1983"
    },
    {
      "key": "2019111905054328500_REF45",
      "doi-asserted-by": "crossref",
      "unstructured": "Castelli-Gair J, Akam M. How the Hox gene Ultrabithorax specifies two different segments: the significance of spatial and temporal regulation within metameres. Development.1995;121: 2973-2982.",
      "DOI": "10.1242/dev.121.9.2973"
    },
    {
      "key": "2019111905054328500_REF46",
      "doi-asserted-by": "crossref",
      "unstructured": "Kawagoe H, Kawagoe R, Sano K. Targeted down-regulation of MLL-AF9 with antisense oligodeoxyribonucleotide reduces the expression of the HOXA7 and -A10 genes and induces apoptosis in a human leukemia cell line, THP-1. Leukemia.2001;15: 1743-1749.",
      "DOI": "10.1038/sj.leu.2402262"
    },
    {
      "key": "2019111905054328500_REF47",
      "doi-asserted-by": "crossref",
      "unstructured": "Rozovskaia T, Feinstein E, Mor O, et al. Upregulation of Meis1 and HoxA9 in acute lymphocytic leukemias with the t(4: 11) abnormality. Oncogene.2001;20: 874-878.",
      "DOI": "10.1038/sj.onc.1204174"
    },
    {
      "key": "2019111905054328500_REF48",
      "doi-asserted-by": "crossref",
      "unstructured": "So CW, Karsunky H, Wong P, Weissman IL, Cleary ML. Leukemic transformation of hematopoietic progenitors by MLL-GAS7 in the absence of Hoxa7 or Hoxa9. Blood.2004;103: 3192-3199.",
      "DOI": "10.1182/blood-2003-10-3722"
    },
    {
      "key": "2019111905054328500_REF49",
      "doi-asserted-by": "crossref",
      "unstructured": "Milne TA, Hughes CM, Lloyd R, et al. Menin and MLL cooperatively regulate expression of cyclin-dependent kinase inhibitors. Proc Natl Acad Sci U S A.2005;102: 749-754.",
      "DOI": "10.1073/pnas.0408836102"
    },
    {
      "key": "2019111905054328500_REF50",
      "doi-asserted-by": "crossref",
      "unstructured": "Xia Z, Popovic R, Chen J, et al. The Mll fusion gene, MLL-AF4, regulates cyclin-dependent kinase inhibitor CDK1B (p27kip1) expression. Proc Natl Acad Sci U S A.2005;102: 14028-14033.",
      "DOI": "10.1073/pnas.0506464102"
    },
    {
      "key": "2019111905054328500_REF51",
      "doi-asserted-by": "crossref",
      "unstructured": "Yokoyama A, Somervaille TCP, Smith KS, Rozenblatt-Rosen O, Meyerson M, Cleary ML. The Menin tumor suppressor protein is an essential oncogenic cofactor for MLL-associated leukemogenesis. Cell.2005;123: 207-218.",
      "DOI": "10.1016/j.cell.2005.09.025"
    },
    {
      "key": "2019111905054328500_REF52",
      "doi-asserted-by": "crossref",
      "unstructured": "Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med.1997;3: 730-737.",
      "DOI": "10.1038/nm0797-730"
    }
  ],
  "container-title": "Blood",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "http://ashpublications.org/blood/article-pdf/108/2/669/470789/zh801406000669.pdf",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "syndication"
    },
    {
      "URL": "http://ashpublications.org/blood/article-pdf/108/2/669/470789/zh801406000669.pdf",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        5,
        6
      ]
    ],
    "date-time": "2023-05-06T20:51:35Z",
    "timestamp": 1683406295000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://ashpublications.org/blood/article/108/2/669/109873/A-murine-MllAF4-knockin-model-results-in-lymphoid"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2006,
        7,
        15
      ]
    ]
  },
  "references-count": 52,
  "journal-issue": {
    "issue": "2",
    "published-print": {
      "date-parts": [
        [
          2006,
          7,
          15
        ]
      ]
    }
  },
  "URL": "http://dx.doi.org/10.1182/blood-2005-08-3498",
  "relation": {},
  "ISSN": [
    "0006-4971",
    "1528-0020"
  ],
  "subject": [],
  "published": {
    "date-parts": [
      [
        2006,
        7,
        15
      ]
    ]
  }
}