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HAX-1 expression in human B lymphoma

Leukemia volume 25, pages 868–872 (2011)Cite this article

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HS-1-associated protein X-1 (HAX-1) was originally identified as a 35 kDa protein that interacts with HS-1, a Src kinase substrate, and was suggested to have a role in B-cell signal transduction.1 HAX-1 is ubiquitously expressed in murine and human tissues and seems to be predominantly localized to mitochondria, and to a lesser extent to the endoplasmic reticulum and nuclear membrane. Previous studies have disclosed homozygous mutations in the HAX1 gene in patients with the autosomal recessive form of severe congenital neutropenia or Kostmann disease, indicating a critical role for HAX-1 in the regulation of myeloid progenitor cell survival in the bone marrow.2 More recent studies point to a critical role of HAX-1 in B-cell development, at least in mice.3 HAX-1 was initially suggested to display homology with BCL-2, and several studies have implicated HAX-1 in the regulation of apoptosis.

Next, we examined the expression of HAX-1 protein in a series of paraffin-embedded diagnostic samples from 50 patients with B-cell lymphoma (Table 1) retrieved from archives of the Department of Pathology, Karolinska University Hospital, Stockholm. Diagnosis was established according to the WHO 2008 classification. The diagnosis of Burkitt's lymphoma was confirmed by fluorescence in situ hybridization for the t(8;14) translocation. The panel included six follicular (FC) lymphoma samples selected from a previously published cohort that we have studied using microarray gene expression profiling.6 On the basis of the microarray data, we selected three samples with high expression and three with low expression of HAX1 mRNA for immunohistochemical studies. Biopsies of reactive tonsils and lymph nodes were used as controls. These studies were approved by the ethical committee at Karolinska Institutet.

Table 1 HAX-1 and BCL-2 protein expression in B-cell lymphoma
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References

  1. Suzuki Y, Demoliere C, Kitamura D, Takeshita H, Deuschle U, Watanabe T . HAX-1, a novel intracellular protein, localized on mitochondria, directly associates with HS1, a substrate of Src family tyrosine kinases. J Immunol 1997; 158: 2736–2744.

    CAS  PubMed  Google Scholar 

  2. Klein C, Grudzien M, Appaswamy G, Germeshausen M, Sandrock I, Schäffer AA et al. HAX-1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease). Nat Genet 2007; 39: 86–92.

    Article  CAS  Google Scholar 

  3. Peckl-Schmid D, Wolkerstorfer S, Königsberger S, Achatz-Straussberger G, Feichtner S, Schwaiger E et al. HAX1 deficiency: impact on lymphopoiesis and B-cell development. Eur J Immunol 2010; 40: 3161–3172.

    Article  CAS  Google Scholar 

  4. Ramsay AG, Keppler MD, Jazayeri M, Thomas GJ, Parsons M, Violette S et al. HS1-associated protein X-1 regulates carcinoma cell migration and invasion via clathrin-mediated endocytosis of integrin αvβ6 . Cancer Res 2007; 67: 5275–5284.

    Article  CAS  Google Scholar 

  5. Trebinska A, Rembiszewska A, Ciosek K, Ptaszynski K, Rowinski S, Kupryjanczyk J et al. HAX-1 overexpression, splicing and cellular localization in tumors. BMC Cancer 2010; 10: 76.

    Article  Google Scholar 

  6. Björck E, Ek S, Landgren O, Jerkeman M, Ehinger M, Björkholm M et al. High expression of cyclin B1 predicts a favorable outcome in patients with follicular lymphoma. Blood 2005; 105: 2908–2915.

    Article  Google Scholar 

  7. Kilpinen S, Autio R, Ojala K, Iljin K, Bucher E, Sara H et al. Systematic bioinformatic analysis of expression levels of 17,330 human genes across 9,783 samples from 175 types of healthy and pathological tissues. Genome Biol 2008; 9: R139.

    Article  Google Scholar 

  8. Lukk M, Kapushesky M, Nikkilä J, Parkinson H, Goncalves A, Huber W et al. A global map of human gene expression. Nat Biotechnol 2010; 28: 322–324.

    Article  CAS  Google Scholar 

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Acknowledgements

These studies were supported by the Swedish Cancer Foundation, Swedish Children's Cancer Foundation, Swedish Cancer and Allergy Foundation, and the Stockholm County Council (ALF project).

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  1. A Kwiecinska and A Ottosson-Wadlund: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, Karolinska University Hospital, Stockholm, Sweden

    A Kwiecinska & A Porwit

  2. Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

    A Ottosson-Wadlund, R Ceder, R C Grafström & B Fadeel

  3. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

    E Björck & M Nordenskjöld

  4. VTT Technical Research Centre of Finland, Medical Biotechnology, Turku, Finland

    R C Grafström

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  1. A Kwiecinska
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Correspondence to B Fadeel.

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Kwiecinska, A., Ottosson-Wadlund, A., Ceder, R. et al. HAX-1 expression in human B lymphoma. Leukemia 25, 868–872 (2011). https://doi.org/10.1038/leu.2010.321

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