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.

  • Letter to the Editor
  • Published:

CD7/CD56-positive acute myeloid leukemias are characterized by constitutive phosphorylation of the NF-kB subunit p65 at Ser536

Leukemia volume 21, pages 1305–1306 (2007)Cite this article

CD7/CD56 myeloid/natural killer acute leukemia represents a novel rare distinct hematologic neoplasia.1 According to its immunologic markers, it is classified as an acute myeloid leukemia (AML) although its clinical presentation is that typical of lymphomas. In particular, CD7/CD56 AML is characterized by an important extramedullary involvement with mediastinal masses and/or peripheral lymphoadenopathies in spite of a generally modest peripheral leucocytosis. Analysis of leukemic blasts and immunohystochemistry of adenopathies are positive for the expression of both myeloid and NK markers (CD7, CD33, CD34, CD56 and frequently HLA-DR). All rare patients relapsed or were refractory to therapies, suggesting that this disease is particularly resistant to the conventional AML chemotherapy. Premature relapse after allogenic bone marrow transplantation have also been described.1

NF-kB is a transcription factor, which is generally composed of the p65/p50 heterodimer. In resting cells, NF-kB is retained into the cytoplasm by the inhibitory protein IkB-α. Upon stimulation, IkB-α becomes degraded and free NF-kB translocates into the nucleus, where it regulates the expression of several genes involved in survival and proliferation. NF-kB has been described as an essential transcription factor in tumorigenesis. In particular, it is believed to be necessary for myeloid leukemogenesis.2 Recently, it has been demonstrated that NF-kB could be activated via a non-canonical pathway.3, 4, 5 At least five kinases are responsible for the phosphorylation of p65 at Ser536.4 This phosphorylated form of p65 is no longer subject to IkB-α inhibition and does not bind to p50. Moreover, phospho-S536-p65 can translocate to the nucleus independently to conventional stimuli, where it may regulate the expression of genes which appear to be different with respect to those regulated by IkB-α-mediated NF-kB activation.4 In the lymphoblastic lymphoma cell line Jurkat and in primary T-cell lymphocytes, p65 is constitutively phosphorylated at Ser536.5

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

Figure 1

References

  1. Suzuki R, Yamamoto K, Seto M, Kagami Y, Ogura M, Yatabe Y et al. CD7 and CD56 myeloid/natural killer cell precursor acute leukemia: a distinct hematolymphoid disease entity. Blood 1997; 90: 2417–2428.

    CAS  PubMed  Google Scholar 

  2. Guzman ML, Neering SJ, Upchurch D, Grimes B, Howard DS, Rizzieri DA et al. Nuclear factor-kappaB is constitutively activated in primitive human acute myelogenous leukemia cells. Blood 2001; 98: 2301–2307.

    Article  CAS  PubMed  Google Scholar 

  3. Mattioli I, Sebald A, Bucher C, Charles RP, Nakano H, Doi T et al. Transient and selective NF-kB p65 Serine 536 phosphorylation induced by T cell costimulation is mediated by IkB kinase and controls the kinetics of p65 nuclear import. J Immunol 2004; 172: 6336–6344.

    Article  CAS  PubMed  Google Scholar 

  4. Buss H, Dorrie A, Schmitz ML, Hoffmann E, Resch K, Kracht M . Constitutive and interleukin-1-inducible phosphorylation of p65 NF-{kappa}B at serine 536 is mediated by multiple protein kinases including I{kappa}B kinase (IKK)-{alpha}, IKK{beta}, IKK{epsilon}, TRAF family member-associated (TANK)-binding kinase 1 (TBK1), and an unknown kinase and couples p65 to TATA-binding protein-associated factor II31-mediated interleukin-8 transcription. J Biol Chem 2004; 279: 55633–55643.

    Article  CAS  PubMed  Google Scholar 

  5. Sasakil CY, Barberi TJ, Ghosh P, Longo DL . Phosphorylation of RelA/p65 on Serine 536 defines an IkB-α independent NF-kB pathway. J Biol Chem 2005; 280: 34538–34547.

    Article  Google Scholar 

  6. Morotti A, Cilloni D, Messa F, Arruga F, Defilippi I, Carturan S et al. Valproate enhances imatinib-induced growth arrest and apoptosis in chronic myeloid leukemia cells. Cancer 2006; 106: 1188–1196.

    Article  CAS  PubMed  Google Scholar 

  7. Baumgartner B, Weber M, Quirling M, Fischer C, Page S, Adam M et al. Increased IkappaB kinase activity is associated with activated NF-kappaB in acute myeloid blasts. Leukemia 2002; 16: 2062–2071.

    Article  CAS  PubMed  Google Scholar 

  8. Song Y-J, Jen K-Y, Soni V, Kieff E, Cahir-McFarland E . IL-1 receptor-associated kinase 1 is critical for latent membrane protein 1-induced p65/RelA Serine 536 phosphorylation and NF-{kappa}B activation. PNAS 2006; 103: 2689–2694.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work has been supported by grants from AIRC (Associazione Italiana per la Ricerca sul Cancro), CNR (Progetto Finalizzato Oncologia), MURST-COFIN 2005, AIL (Associazione Italiana contro le Leucemie) and by Regione Piemonte.

Author information

Authors and Affiliations

  1. Department of Clinical and Biological Sciences, University of Turin, Turin, Italy

    A Morotti, G Parvis, D Cilloni, M Bosa, F Messa, F Arruga, I Defilippi, R Catalano, V Rosso, S Carturan, E Bracco, A Guerrasio & G Saglio

  2. Department of Pathology, Ospedale San Luigi, Orbassano, Italy

    U Familiari

  3. Laboratory of Clinical Pathology, Ospedale San Luigi, Orbassano, Italy

    M Pautasso

Authors
  1. A Morotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G Parvis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D Cilloni
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. U Familiari
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M Pautasso
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M Bosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. F Messa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. F Arruga
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. I Defilippi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. R Catalano
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. V Rosso
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. S Carturan
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. E Bracco
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. A Guerrasio
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. G Saglio
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A Morotti.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Morotti, A., Parvis, G., Cilloni, D. et al. CD7/CD56-positive acute myeloid leukemias are characterized by constitutive phosphorylation of the NF-kB subunit p65 at Ser536. Leukemia 21, 1305–1306 (2007). https://doi.org/10.1038/sj.leu.2404581

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2404581

Search

Advanced search

Quick links