Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

MLL AT-hook sequence is strongly conserved in infant acute leukemia with or without MLL gene rearrangement

Leukemia volume 17, pages 1432–1433 (2003)Cite this article

TO THE EDITOR

Mixed lineage leukemia (MLL) gene disruptions, especially translocations t(4;11)(q21; q 23) and t(11;19)(q23; p13), account for 60–70% of the rearrangements found in infant acute leukemia (AL).1 In such translocation events, the N-terminal region of MLL is maintained, while the MLL and fusion partner C-terminals are exchanged. The MLL gene located at 11q23 encodes for a predicted 431 kDa protein that is proteolytically processed into two fragments (300 and 180 kDa) accordingly.2 fusion proteins that lack the cleavage site are thought to play an important role in the leukemogenesis process. The MLL gene has been extensively characterized and several important functional domains have been isolated including the central PHD finger and C-terminal SET domain. (reviewed in Ayton and Clearly3) N-terminal domains include the AT hooks and a region with homology to DNA methyltransferase. Functional studies have tried to establish the role of these domains in the malignant process.3,4 Three short motifs, known as AT hooks are thought to mediate the targeting of MLL to its nuclear site4 and permit specific binding to the minor groove of AT-rich DNA. These motifs, the theme of our study, are thought to be critical for leukemogenesis4 and may indirectly stabilize protein–DNA interactions by inducing conformational changes, such as DNA bending, which may in turn effect the binding of specific transacting factors or facilitate the protein–protein interactions that control gene expression. Taken together, this information suggested to us a possible role for mutations in the AT-hook region being a basis for cell transformation in those patients without detectable MLL involvement. In order to fully characterize the possible molecular changes in the MLL AT-hook motifs, we have studied the AT-hook DNA sequence and its variability in cases of infant AL.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Biondi A, Cimino G, Peters R, Pui C-H . Biological and therapeutics aspects of infant leukemia. Blood 2000; 96: 24–33.

    CAS  PubMed  Google Scholar 

  2. Yokoyama K, Kitabayashi I, Ayton PM, Cleary ML, Ohki M . Leukemia proto-oncoprotein MLL is proteolytically processed into two fragments with opposite transcriptional properties. Blood 2002; 100: 3710–3718.

    Article  CAS  PubMed  Google Scholar 

  3. Ayton PM, Cleary ML . Molecular mechanisms of leukemogenesis mediated by MLL fusion proteins. Oncogene 2001; 20: 5695–5707.

    Article  CAS  PubMed  Google Scholar 

  4. Slany RK, Lavau C, Cleary ML . The oncogenic capacity of HRX-ENL requires the trancriptional transactivation activity of ENL and the DNA binding motifs of HRX. Mol Cell Biol. 1998; 18: 122–129.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Caslini C, Alarcón AS, Hess JL, Murti KG, Biondi A . The amino terminus targets the mixed linage leukemia (MLL) protein to the nucleolus, nuclear matrix and mitotic chromosomal scaffolds. Leukemia 2000; 14: 1898–1908.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ford AM, Ridge SA, Cabrera ME, Mahmoud H, Steel CM, Chan LC, Greaves MF . In utero rearrangements in the trithorax-related oncogene in infant leukaemias. Nature 1993; 363: 358–360.

    Article  CAS  PubMed  Google Scholar 

  7. Gale KB, Ford AM, Repp R, Borkhardt A, Keller C, Eden OB, Greaves MF . Backtracking leukemia to birth: identification of clonotypic gene fusion sequences in neonatal blood spots. Proc Natl Acad Sci USA. 1997; 94: 13950–13954.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Alexander FE, Patheal SH, Biondi A, Brandalise S, Cabrera ME, Chan LC et al. Transplacental chemical exposure and risk of infant leukemia with MLL gene fusion. Cancer Res. 2001; 61: 2542–2546.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratório de Marcadores Celulares, Serviço de Hematologia, Instituto Nacional de Câncer, Rio de Janeiro, Brasil

    C M T Macrini, M S Pombo-de-Oliveira & G Alves

  2. Leukaemia Research Fund Centre, Institute of Cancer Research, London, UK

    A M Ford

Authors
  1. C M T Macrini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M S Pombo-de-Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A M Ford
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G Alves
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Macrini, C., Pombo-de-Oliveira, M., Ford, A. et al. MLL AT-hook sequence is strongly conserved in infant acute leukemia with or without MLL gene rearrangement. Leukemia 17, 1432–1433 (2003). https://doi.org/10.1038/sj.leu.2402966

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2402966

Search

Advanced search

Quick links