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  • Letter to the Editor
  • Published:

Reply to ‘CD49d in B-cell chronic lymphocytic leukemia: correlated expression with CD38 and prognostic relevance’ by Zucchetto et al.

Leukemia volume 20, page 528 (2006)Cite this article

We are gratified to see the additional data of Zucchetto and colleagues that further support the association of α4 integrin (CD49d) and CD38 expression in B-CLL.1, 2, 3 Our recently published study discovered the link between CD38 expression and CD49d on leukemic CLL B cells as a result of gene expression profiling.2 Using a novel method of surface antigen expression profiling to define the immunophenotype of specific B-CLL subsets, Zucchetto et al.3 also recently reported that overexpression of CD49d is frequently observed in association with the above average expression of CD38, CD29, and CD49e. The additional data included in the Letter to the Editor extend both those studies2, 3 by showing that CD49d expression correlates with the clinically important parameters and outcomes including advanced Rai stage at the time of diagnosis, unfavorable IgVH mutational status, time to progression, and overall survival. Of note, we defined CD38 positivity according to the mean fluorescence intensity (MFI) ratio of CD38-staining in relation to control staining2 whereas Zucchetto et al.1, 3 used a cutoff value of 30%. It would, therefore, be informative to compare results with these investigators to determine how many of their patients who are discordantly CD38low/CD49dhigh would have been considered CD38+ using the methods of our study, that is, displaying CD38 staining at levels above control staining. Moreover, it would also be of interest to see if the association of CD38 and/or CD49d expression has an even greater positive correlation with the Rai stage at the time of blood sampling as compared to the Rai stage at the time of diagnosis.

When reviewing our data in the context of Zucchetto et al. report,1 it could be suggested that CD38 and CD49d may act synergistically to confer aggressive disease behavior. It is known that integrins such as CD49d require Ca++ to function as adhesion molecules in their role promoting homing and migration of lymphocytes. It is also known that CD38 functions as an ectoenzyme, catalyzing the conversion of NAD+ to cADPR, a potent Ca++ mobilizer.4 Therefore, it is plausible that their coexpression could facilitate the homing of CLL B cells to tissue sites with a more favorable environmental milieu that in turn promotes more rapid leukemic B-cell growth and longer survival, a notion congruent with the finding that the level of α4 integrin expression is associated with the presence of clinically detectable lymphadenopathy.5 It would also be interesting to determine if the function of integrins expressed on CLL B cells is impaired in CD38− but not in CD38+ CLL B cells. Given the provocative association of these two antigens on CLL B cells now demonstrated by both groups,1, 2, 3 and the demonstration that CD38 and CD49d are complementary adverse prognostic factors in B-CLL,1 it is tempting to speculate that these molecules play an important role in more progressive clinical disease. In summary, these reports suggest simultaneous assessment of both antigens may refine the usefulness of CD38 as a useful prognostic tool in B-CLL.

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References

  1. Zucchetto A, Bomben R, Dal Bo M, Bulien P, Benedetti D, Nanni P et al. CD49d in B-cell chronic lymphocytic leukemia: correlated expression with CD38 and prognostic relevance. Leukemia 2006 (this volume and edition).

  2. Pittner BT, Shanafelt TD, Kay NE, Jelinek DF . CD38 expression levels in chronic lymphocytic leukemia B cells are associated with activation marker expression and differential responses to interferon stimulation. Leukemia 2005, Oct 6; [E-pub ahead of print].

  3. Zucchetto A, Sonego P, Degan M, Bomben R, Dal Bo M, Russo S et al. Signature of B-CLL with different prognosis by shrunken centroids of surface antigen expression profiling. J Cell Physiol 2005; 204: 113–123.

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  5. Till KJ, Lin K, Zuzel M, Cawley JC . The chemokine receptor CCR7 and alpha4 integrin are important for migration of chronic lymphocytic leukemia cells into lymph nodes. Blood 2002; 99: 2977–2984.

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Authors and Affiliations

  1. Department of Immunology, Mayo Clinic College of Medicine, Mayo Graduate School, Rochester, MN, USA

    B T Pittner & D F Jelinek

  2. Division of Hematology, Department of Internal Medicine, Mayo Clinic College of Medicine, Mayo Graduate School, Rochester, MN, USA

    T D Shanafelt & N E Kay

Authors
  1. B T Pittner
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  2. T D Shanafelt
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  3. N E Kay
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  4. D F Jelinek
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Pittner, B., Shanafelt, T., Kay, N. et al. Reply to ‘CD49d in B-cell chronic lymphocytic leukemia: correlated expression with CD38 and prognostic relevance’ by Zucchetto et al.. Leukemia 20, 528 (2006). https://doi.org/10.1038/sj.leu.2404088

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