CD200 as a prognostic factor in acute myeloid leukaemia (original) (raw)

Leukemia volume 21, pages 566–568 (2007)Cite this article

The CD200 gene (aka MOX-2, OX-2) is located on chromosome 3 and encodes a type-1 membrane glycoprotein.1 This protein belongs to the immunoglobulin superfamily and is expressed on many different cell types including T and B lymphocytes and dendritic cells.2 CD200 binds multiple membrane receptor isoforms (CD200R) which have a more tissue restricted expression.3, 4 The best characterized isoform, CD200R1, has a longer cytoplasmic tail containing three conserved tyrosine residues that can be phosphorylated.1 These phosphorylated residues interact with signalling adaptor molecules such as Shc, suggesting that the CD200R1 can signal upon binding CD200 ligand providing a more localized response than that provided by cytokines.5 Although CD200(−/−)-deficient mice appear grossly normal and live a normal lifespan, they are susceptible to tissue-specific autoimmunity, suggesting that the function of this protein is to induce immune suppression through the CD200R.6 CD200 also appears to have an alternative role in regulating osteoclast development.7 In leukaemia, CD200 has been shown to be upregulated in B cells from patients with chronic lymphocytic leukemia.8 More recently, CD200 has been shown to be an independent prognostic factor for patients with multiple myeloma.9 In this latter study, expression of CD200 was associated with a bad prognosis. Here we report that in acute myeloid leukaemia (AML), there is a correlation between CD200 expression and the presence of the core binding factor (CBF) associated abnormalities, t(8;21) and inv(16). However, at the same time CD200 expression was linked to worse overall survival in other AML subsets. These data indicate that CD200 is also of prognostic value in AML.

We also examined the correlation of level of CD200 gene expression with AML subtype (Figure 1c). As might be expected from the high frequency of _CD200_present patients in t(8;21) leukaemias, these patients also significantly overexpressed CD200 by 1.8-fold when compared to FAB-M2 patients without this cytogenetic abnormality (_P_=0.03). Induction of CD200 may be a direct consequence of AML1-ETO expression, because human primary cells transduced with this fusion gene also overexpress CD200 (A.Tonks, submitted). Furthermore, patients expressing an inv(16) mutation (generally associated with FAB-M4) also significantly overexpressed CD200 when compared to M4 patients without an inv(16) mutation (1.3-fold; _P_=0.02). Additionally, Cox regression shows that, when adjusted for the type of leukaemia, the level of CD200 expression was significantly associated with worse overall survival (_P_=0.04). This data suggests that CD200 may have independent prognostic value in AML.

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

Access options

Subscribe to this journal

Receive 12 print issues and online access

$259.00 per year

only $21.58 per issue

Buy this article

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

Additional access options:

References

  1. Wright GJ, Puklavec MJ, Willis AC, Hoek RM, Sedgwick JD, Brown MH et al. Lymphoid/neuronal cell surface OX2 glycoprotein recognizes a novel receptor on macrophages implicated in the control of their function. Immunity 2000; 13: 233–242.
    Article CAS PubMed Google Scholar
  2. Barclay AN, Wright GJ, Brooke G, Brown MH . CD200 and membrane protein interactions in the control of myeloid cells. Trends Immunol 2002; 23: 285–290.
    Article CAS PubMed Google Scholar
  3. Wright GJ, Cherwinski H, Foster-Cuevas M, Brooke G, Puklavec MJ, Bigler M et al. Characterization of the CD200 receptor family in mice and humans and their interactions with CD200. J Immunol 2003; 171: 3034–3046.
    Article CAS PubMed Google Scholar
  4. Gorczynski RM, Chen Z, Lee L, Yu K, Hu J . Anti-CD200R ameliorates collagen-induced arthritis in mice. Clin Immunol 2002; 104: 256–264.
    Article CAS PubMed Google Scholar
  5. Songyang Z, Margolis B, Chaudhuri M, Shoelson SE, Cantley LC . The phosphotyrosine interaction domain of SHC recognizes tyrosine-phosphorylated NPXY motif. J Biol Chem 1995; 270: 14863–14866.
    Article CAS PubMed Google Scholar
  6. Hoek RM, Ruuls SR, Murphy CA, Wright GJ, Goddard R, Zurawski SM et al. Down-regulation of the macrophage lineage through interaction with OX2 (CD200). Science 2000; 290: 1768–1771.
    Article CAS PubMed Google Scholar
  7. Lee L, Liu J, Manuel J, Gorczynski RM . A role for the immunomodulatory molecules CD200 and CD200R in regulating bone formation. Immunol Lett 2006; 105: 150–158.
    Article CAS PubMed Google Scholar
  8. McWhirter JR, Kretz-Rommel A, Saven A, Maruyama T, Potter KN, Mockridge CI et al. Antibodies selected from combinatorial libraries block a tumor antigen that plays a key role in immunomodulation. Proc Natl Acad Sci USA 2006; 103: 1041–1046.
    Article CAS PubMed PubMed Central Google Scholar
  9. Moreaux J, Hose D, Reme T, Jourdan E, Hundemer M, Legouffe E et al. CD200 is a new prognostic factor in Multiple Myeloma. Blood First Edition Paper, prepublished online August 31 2006; DOI:10.1182/blood-2006-06-029355.
    Article CAS PubMed Google Scholar

Download references

Acknowledgements

We thank Amanda Gilkes and Megan Musson (Cardiff University) for their technical assistance in processing microarray samples. We are grateful to the MRC for access to material from patients enrolled in the NCRI clinical trials. AT was supported by Leukaemia Research, UK.

Author information

Authors and Affiliations

  1. Department of Haematology, School of Medicine, Cardiff University, Cardiff, UK
    A Tonks, R Hills, P White, B Rosie, K I Mills, A K Burnett & R L Darley

Authors

  1. A Tonks
    You can also search for this author inPubMed Google Scholar
  2. R Hills
    You can also search for this author inPubMed Google Scholar
  3. P White
    You can also search for this author inPubMed Google Scholar
  4. B Rosie
    You can also search for this author inPubMed Google Scholar
  5. K I Mills
    You can also search for this author inPubMed Google Scholar
  6. A K Burnett
    You can also search for this author inPubMed Google Scholar
  7. R L Darley
    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence toA Tonks.

Rights and permissions

About this article

Cite this article

Tonks, A., Hills, R., White, P. et al. CD200 as a prognostic factor in acute myeloid leukaemia.Leukemia 21, 566–568 (2007). https://doi.org/10.1038/sj.leu.2404559

Download citation