Skip to main content
SpringerLink
Log in

The Stem Cell Leukaemia Gene: A Critical Regulator of Haemopoiesis Vasculogenesis

  • Conference paper
Acute Leukemias IX

Part of the book series: Haematology and Blood Transfusion Hämatologie und Bluttransfusion ((HAEMATOLOGY,volume 41))

  • 133 Accesses

Abstract

The SCL gene (also known as TAL1) was first identified as a T-cell oncogene. (Begley and Green 1999). It encodes a basic helix-loophelix (bHLH) protein which is normally expressed in blood endothelium and in specific regions of the central nervous system (Green et al. 1992; Hwang et al. 1993; Cross et al. 1994; Kallianpur et al. 1994; Drake et al. 1997). Within the haematopoietic system SCL is expressed in committed erythroid, mast megakaryocytic cells as well as in primitive CD34+ cell lines and bone marrow progenitors. Antisense and over-expression studies have suggested that SCL modulates proliferation and self-renewal of multipotent haemopoietic cells (Green et al. 1991) and also acts as a positive regulator of erythroid differentiation (Aplan et al. 1992). SCL null mice completely lacked yolk sac haemopoiesis (Robb et al. 1995; Shivdasani et al. 1995) and SCL-null ES cells also failed to contribute to any definitive haemopoietic lineage (Porcher et al. 1996; Robb et al. 1996). Existing data therefore demonstrate that SCL plays a pivotal role in the formation or behaviour of haemopoietic stem cells and underline the striking similarities between the role of SCL in haemopoiesis and the function of other bHLH proteins in muscle and neural development.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 74.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Aplan PD, Nakahra K, Orkin SH, and Kirsch IR (1992) The SCL gene product: a positive regulator of erythroid differentiation. EMBO J 11: 4073 – 4081

    PubMed  CAS  Google Scholar 

  • Begley CG and Green AR (1999) The SCL gene: from case report to critical hematopoietic regulator. Blood 93: 2760 – 2770

    PubMed  CAS  Google Scholar 

  • Bockamp EO, McLaughlin F, Murrell AM, Göttgens B, Robb L, Begley CG, and Green AR (1995) Lineagerestricted regulation of the murine SCL/TAL-1 promoter. Blood 86: 1502 – 1514

    PubMed  CAS  Google Scholar 

  • Bockamp EO, McLaughlin F, Göttgens B, Murrell AM, Elefanty AG, and Green AR (1997) Distinct mechanisms direct SCL/tal-1 expression in erythroid cells and CD34 positive primitive myeloid cells. J Biol Chem 272: 8781 – 8790

    Article  PubMed  CAS  Google Scholar 

  • Bockamp EO, Fordham JL, Gottgens B, Murrell AM, Sanchez MJ, and Green AR (1998) Transcriptional regulation of the stem cell leukemia gene by PU.1 and Elf-1. J Biol Chem 273: 29032 – 29042

    Article  PubMed  CAS  Google Scholar 

  • Codias EK, Cray C, Baler RD, Levy RB, and Malek TR (1989) Expression of Ly-6A/E alloantigens in thymocyte and T-lymphocyte subsets: variability related to the Ly-6a and Ly-6b haplotypes. Immunogenetics 29: 98 – 107

    Article  PubMed  CAS  Google Scholar 

  • Cross MA, Heyworth CM, Murrell AM, Bockamp EO, Cobley UT, Dexter TM, and Green AR (1994) Expression of lineage restricted transcription factors precedes lineage specific differentiation in a multipotent haemopoietic progenitor cell line. Oncogene 9: 3013 – 3016

    PubMed  CAS  Google Scholar 

  • Domen J, Cheshier SH, and Weissman IL (2000) The role of apoptosis in the regulation of hematopoietic stem cells: Overexpression of Bcl-2 increases both their number and repopulation potential. J Exp Med 191: 253 – 264

    Article  PubMed  CAS  Google Scholar 

  • Drake CJ, Brandt SJ, Trusk TC, and Little CD (1997) TAL1/SCL is expressed in endothelial progenitor cells/angioblasts and defines a dorsal-to-ventral gradient of vasculogenesis. Developmental Biology 192: 17 – 30

    Article  PubMed  CAS  Google Scholar 

  • Faloon P, Arentson E, Kazarov A, Deng CX, Porcher C, Orkin S, and Choi K (2000) Basic fibroblast growth factor positively regulates hematopoietic development. Development 127: 1931 – 1941

    PubMed  CAS  Google Scholar 

  • Gering M, Rodaway ARF, Göttgens B, Patient RK, and Green AR (1998) The SCL gene specifies haemangioblast development from early mesoderm. EMBO J 17: 4029 – 4045

    Article  PubMed  CAS  Google Scholar 

  • Göttgens B, McLaughlin F, Bockamp EO, Fordham JL, Begley CG, Kosmopoulos K, Elefanty AG, and Green AR (1997) Transcription of the SCL gene in erythroid and CD34 positive primitive myeloid cells is controlled by a complex network of lineagerestricted chromatin-dependent and chromatinindependent regulatory elements. Oncogene 15: 2419 – 2428

    Article  PubMed  Google Scholar 

  • Göttgens B, Barton LM, Gilbert JG, Bench AJ, Sanchez MJ, Bahn S, Mistry S, Grafham D, McMurray A, Vaudin M, Amaya E, Bentley DR, and Green AR (2000) Analysis of vertebrate SCL loci identifies conserved enhancers. Nat Biotechnol 18: 181 – 186

    Article  PubMed  Google Scholar 

  • Göttgens B, Gilbert JG, Barton LM, Grafham D, Rogers J, Bentley DR, and Green AR (2001) Long-range comparison of human and mouse SCL loci: localized regions of sensitivity to restriction endonucleases correspond precisely with peaks of conserved noncoding sequences. Genome Res 11: 87 – 97

    Article  PubMed  Google Scholar 

  • Green AR, De Luca E, and Begley CG (1991) Antisense SCL suppresses self-renewal and enhances spontaneous erythroid differentiation of the human leukaemic cell line K562. EMBO J 10: 4153 – 4158

    PubMed  CAS  Google Scholar 

  • Green AR, Visvader J, Lints T, Harvey R, and Begley CG (1992) SCL is co-expressed with GATA-1 in haemopoietic cells but is also expressed in developing brain. Oncogene 7: 653 – 660

    PubMed  CAS  Google Scholar 

  • Hwang LY, Siegelman M, Davis L, Oppenheimer-Marks N, and Baer R (1993) Expression of the TAL-1 proto-oncogene in cultured endothelial cells and blood vessels of the spleen. Oncogene 8: 3043 – 3046

    PubMed  CAS  Google Scholar 

  • Kallianpur AR, Jordan JE, and Brandt SJ (1994) The SCL/TAL-1 gene is expressed in progenitors of both the hematopoietic and vascular systems during embryogenesis. Blood 83: 1200 – 1208

    PubMed  CAS  Google Scholar 

  • Liao EC, Paw BH, Oates AC, Pratt SJ, Postlethwait JH, and Zon LI (1998) SCLITal-1 transcription factor acts downstream of cloche to specify hematopoietic and vascular progenitors in zebrafish. Genes & Devel 12: 621 – 626

    Article  CAS  Google Scholar 

  • Miles C, Sanchez MJ, Sinclair A, and Dzierzak E (1997) Expression of the Ly-6E. 1(Sca-1) transgene in adult haematopoietic stem cells and the developing mouse embryo. Development 124: 537 – 547

    PubMed  CAS  Google Scholar 

  • Porcher C, Swat W Rockwell K, Fujiwara Y, Alt FW, and Orkin SH (1996) The T cell leukemia oncoprotein SCLltal-1 is essential for development of all hematopoietic lineages. Cell 86: 47 – 57

    Article  PubMed  CAS  Google Scholar 

  • Robb L, Lyons I, Li R, Hartley L, Kontgen F, Harvey RP, Metcalf D, and Begley CG (1995) Absence of yolk sac hematopoiesis from mice with a targeted disruption of the scl gene. Proc Natl Acad Sci USA 92: 7075 – 7079

    Article  PubMed  CAS  Google Scholar 

  • Robb L, Elwood NJ, Elefanty AG, Köntgen F, Li R, Barnett LD, and Begley CG (1996) The SCL gene product is required for the generation of all hematopoietic lineages in the adult mouse. EMBO J 15: 4123 – 4129

    PubMed  CAS  Google Scholar 

  • Robertson SM, Kennedy M, Shannon JM, and Keller G (2000) A transitional stage in the commitment of mesoderm to hematopoiesis requiring the transcription factor SCLltal-l. Development 127: 2447 – 2459

    PubMed  CAS  Google Scholar 

  • Sanchez MJ, Göttgens B, Sinclair AM, Stanley M, Begley CG, Hunter S, and Green AR (1999) An SCL 3’ enhancer targets developing endothelium together with embryonic and adult haematopoietic progenitors. Development 126: 3891 – 3904

    PubMed  CAS  Google Scholar 

  • Shivdasani RA, Mayer EL, and Orkin SH (1995) Absence of blood formation in mice lacking the T-cell leukemia oncoprotein tal-1/SCL. Nature 373: 432 – 434

    Article  PubMed  CAS  Google Scholar 

  • Sinclair AM, Göttgens B, Barton LM, Stanley ML, Pardanaud L, Klaine M, Gering M, Bockamp E0, Sanchez MJ, Bench AJ, Fordham JL, Bahn S, and Green AR (1999) Distinct 5’ SCL enhancers direct transcription to developing brain, spinal cord, and endothelium: Neural Expression is mediated by GATA factor binding sites. Dev Biol 209:128–142 Spangrude GJ, Heimfeld S, and Weissman IL (1988) Purification and characterisation of mouse hematopoietic stem cells. Science 241: 58 – 62

    Google Scholar 

  • Visvader JE, Fujiwara Y, and Orkin SH (1998) Unsuspected role for the T-cell leukemia protein SCLltal-1 in vascular development. Genes & Devel 12: 473 – 479.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Haematology, Wellcome Trust Centre for Molecular Mechanisms in Disease, CIMR, University of Cambridge, Cambridge, CB2 2XY, USA

    A. R. Green

Authors
  1. A. R. Green
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Klinikum Grofihadern Med. Klinik III, Ludwig-Maximilians-Universität, Marchioninistr. 15, 81377, München, Germany

    Wolfgang Hiddemann , Torsten Haferlach  & Michael Unterhalt ,  & 

  2. Department of Internal Medicine A, University of Münster, Albert-Schweitzer-Str. 33, 48149, Münster, Germany

    Thomas Büchner

  3. Department of Pediatric Hematology/Oncologic, University of Münster, Albert-Schweitzer-Str. 33, 48149, Münster, Germany

    Jörg Ritter

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Green, A.R. (2003). The Stem Cell Leukaemia Gene: A Critical Regulator of Haemopoiesis Vasculogenesis. In: Hiddemann, W., Haferlach, T., Unterhalt, M., Büchner, T., Ritter, J. (eds) Acute Leukemias IX. Haematology and Blood Transfusion Hämatologie und Bluttransfusion, vol 41. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59358-1_21

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-59358-1_21

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-63949-4

  • Online ISBN: 978-3-642-59358-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation