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CLL

Grb7 expression and cellular migration in chronic lymphocytic leukemia: a comparative study of early and advanced stage disease

Leukemia volume 18, pages 1948–1950 (2004)Cite this article

Abstract

Grb7, a noncatalytic intracellular adaptor protein involved in cell migration, is overexpressed in certain invasive and metastatic solid tumors. We found a highly significant difference in the level of expression of Grb7 between chronic lymphocytic leukemia (CLL) cells obtained from stage I and stage IV patients (P<0.001). Using semiquantitative RT-PCR, we detected high levels of Grb7 in 88% of stage IV patients vs only 18% in stage I patients. A corresponding increase was found in the in vitro migration of stage IV CLL cells in comparison to stage I cells. The statistically significant difference in the expression of Grb7 between stage IV and stage I patients was preserved even when tested specifically in the ZAP70-positive group (P<0.01). These findings show that Grb7 levels reflect the severity of the disease, and may be used, in conjunction with ZAP70, to predict disease progression.

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References

  1. Chiorazzi N, Ferrarini M . B cell chronic lymphocytic leukemia: lessons learned from studies of the B cell antigen receptor. Annu Rev Immunol 2003; 21: 841–894.

    Article  CAS  Google Scholar 

  2. Cheson BD, Bennett JM, Grever M, Kay N, Keating MJ, O'Brien S et al. National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood 1996; 87: 4990–4997.

    CAS  Google Scholar 

  3. Meinhardt G, Wendtner C-M, Hallek M . Molecular pathogenesis of chronic lymphocytic leukemia: factors and signaling pathways regulating cell growth and survival. J Mol Med 1999; 77: 282–293.

    Article  CAS  Google Scholar 

  4. Burger JA, Tsukada N, Burger M, Zvaifler NJ, Dell'Aquila M, Kipps TJ . Blood-derived nurse-like cells protect chronic lymphocytic leukemia B cells from spontaneous apoptosis through stromal cell-derived factor-1. Blood 2000; 96: 2655–2663.

    CAS  PubMed  Google Scholar 

  5. de la Fuente MT, Casanova B, Garcia-Gila M, Silva A, Garcia-Pardo A . Fibronectin interaction with alpha4beta1 integrin prevents apoptosis in B cell chronic lymphocytic leukemia: correlation with Bcl-2 and Bax. Leukemia 1999; 13: 266–274.

    Article  CAS  Google Scholar 

  6. Han DC, Shen T, Guan J . The Grb7 family proteins: structure, interactions with other signaling molecules and potential cellular functions. Oncogene 2001; 20: 6315–6321.

    Article  CAS  Google Scholar 

  7. Flynn DC . Adaptor proteins. Oncogene 2001; 20: 6270–6272.

    Article  CAS  Google Scholar 

  8. Shachar I, Elliot E, Chasnoff B, Grewal I, Flavell R . Reconstitution of invariant chain function in transgenic mice in vivo by individual p31 and p41 isoforms. Immunity 1995; 3: 373–383.

    Article  CAS  Google Scholar 

  9. Burger JA, Burger M, Kipps TJ . Chronic lymphocytic leukemia B cells express functional CXCR4 chemokine receptors that mediate spontaneous migration beneath bone marrow stromal cells. Blood 1999; 94: 3658–3667.

    CAS  Google Scholar 

  10. Barretina J, Junca J, Llano A, Gutierrez A, Flores A, Blanco J et al. CXCR4 and SDF-1 expression in B-cell chronic lymphocytic leukemia and stage of the disease. Ann Hematol 2003; 82: 500–505.

    Article  CAS  Google Scholar 

  11. Crespo M, Bosch F, Villamor N, Bellosillo B, Colomer D, Rozman M et al. ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. N Engl J Med 2003; 348: 1764–1775.

    Article  CAS  Google Scholar 

  12. Shen TL, Guan JL . Differential regulation of cell migration and cell cycle progression by FAK complexes with Src, PI3K, Grb7 and Grb2 in focal contacts. FEBS Lett 2001; 499: 176–181.

    Article  CAS  Google Scholar 

  13. Tanaka S, Sugimachi K, Kawaguchi H, Saeki H, Ohno S, Wands JR . Grb7 signal transduction protein mediates metastatic progression of esophageal carcinoma. J Cell Physiol 2000; 183: 411–415.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by a grant from the Israeli cancer foundation Abisch-Frenkel Foundation and by a joint grant from the Hebrew university and Kaplan Medical Center. We gratefully acknowledge the staff at the Kaplan Medical Center Hematology Institute, for their support in obtaining the blood samples.

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Author notes

  1. I Shachar: Incumbent of the Alvin and Gertrude Levine Career Development Chair of Cancer Research

Authors and Affiliations

  1. Hematology Institute, Kaplan Medical Center, Rehovot, Israel

    M Haran, S Chebatco, N Harpaz, L Valinsky & A Berrebi

  2. Department of Immunology, Weizmann institute of Science, Rehovot, Israel

    L Flaishon, F Lantner & I Shachar

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  1. M Haran
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  2. S Chebatco
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  3. L Flaishon
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  4. F Lantner
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  5. N Harpaz
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  6. L Valinsky
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  7. A Berrebi
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  8. I Shachar
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Correspondence to M Haran or I Shachar.

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Haran, M., Chebatco, S., Flaishon, L. et al. Grb7 expression and cellular migration in chronic lymphocytic leukemia: a comparative study of early and advanced stage disease. Leukemia 18, 1948–1950 (2004). https://doi.org/10.1038/sj.leu.2403512

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