CoChat
Sign Up
Cited by 426

The DOI matches its Crossref record.

Expression of ZAP-70 is associated with increased B-cell receptor signaling in chronic lymphocytic leukemia

Chen, Liguang, Widhopf, George, Huynh, Lang, Rassenti, Laura, Rai, Kanti R., Weiss, Arthur, Kipps, Thomas J.·2002·Blood
DOI 10.1182/blood-2002-06-1683
Open this paper in CoChat — free account

Abstract

We examined isolated leukemia B cells of patients with chronic lymphocytic leukemia (CLL) for expression of zeta-associated protein 70 (ZAP-70). CLL B cells that have nonmutated immunoglobulin variable region genes (V genes) expressed levels of ZAP-70 protein that were comparable to those expressed by normal blood T cells. In contrast, CLL B cells that had mutated immunoglobulin variable V genes, or that had low-level expression of CD38, generally did not express detectable amounts of ZAP-70 protein. Leukemia cells from identical twins with CLL were found discordant for expression of ZAP-70, suggesting that B-cell expression of ZAP-70 is not genetically predetermined. Ligation of the B-cell receptor (BCR) complex on CLL cells that expressed ZAP-70 induced significantly greater tyrosine phosphorylation of cytosolic proteins, including p72Syk, than did similar stimulation of CLL cells that did not express ZAP-70. Also, exceptional cases of CLL cells that expressed mutated immunoglobulin V genes and ZAP-70 also experienced higher levels tyrosine phosphorylation of such cytosolic proteins following BCR ligation. Following BCR ligation, ZAP-70 underwent tyrosine phosphorylation and became associated with surface immunoglobulin and CD79b, arguing for the involvement of ZAP-70 in BCR signaling. These data indicate that expression of ZAP-70 is associated with enhanced signal transduction via the BCR complex, which may contribute to the more aggressive clinical course associated with CLL cells that express nonmutated immunoglobulin receptors.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1182/blood-2002-06-1683

Cites

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

No references could be resolved yet.

Research works printed but not linked: 35

  1. Fais, 1998, Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors., J Clin Invest., 102, 1515, 10.1172/JCI3009 · DOI
  2. Damle, 1999, Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia., Blood., 94, 1840, 10.1182/blood.V94.6.1840 · DOI
  3. Hamblin, 1999, Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia., Blood., 94, 1848, 10.1182/blood.V94.6.1848 · DOI
  4. Maloum, 2000, Expression of unmutated VH genes is a detrimental prognostic factor in chronic lymphocytic leukemia., Blood., 96, 377, 10.1182/blood.V96.1.377.013k56f_377_379 · DOI
  5. Rosenwald, 2001, Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia., J Exp Med., 194, 1639, 10.1084/jem.194.11.1639 · DOI
  6. Klein, 2001, Gene expression profiling of B cell chronic lymphocytic leukemia reveals a homogeneous phenotype related to memory B cells., J Exp Med., 194, 1625, 10.1084/jem.194.11.1625 · DOI
  7. Taniguchi, 1991, Molecular cloning of a porcine gene syk that encodes a 72-kDa protein-tyrosine kinase showing high susceptibility to proteolysis., J Biol Chem., 266, 15790, 10.1016/S0021-9258(18)98478-4 · DOI
  8. Chan, 1992, ZAP-70: a 70 kd protein-tyrosine kinase that associates with the TCR zeta chain., Cell., 71, 649, 10.1016/0092-8674(92)90598-7 · DOI
  9. Qian, 1997, T cell antigen receptor signal transduction., Curr Opin Cell Biol., 9, 205, 10.1016/S0955-0674(97)80064-6 · DOI
  10. Kane, 2000, Signal transduction by the TCR for antigen., Curr Opin Immunol., 12, 242, 10.1016/S0952-7915(00)00083-2 · DOI · Paper page
  11. Chan, 1994, Differential expression of ZAP-70 and Syk protein tyrosine kinases, and the role of this family of protein tyrosine kinases in TCR signaling., J Immunol., 152, 4758, 10.4049/jimmunol.152.10.4758 · DOI · Paper page
  12. Law, 1994, Molecular cloning of human Syk: a B cell protein-tyrosine kinase associated with the surface immunoglobulin M-B cell receptor complex., J Biol Chem., 269, 12310, 10.1016/S0021-9258(17)32717-5 · DOI · Paper page
  13. Kong, 1995, Reconstitution of Syk function by the ZAP-70 protein tyrosine kinase., Immunity., 2, 485, 10.1016/1074-7613(95)90029-2 · DOI
  14. Toyabe, 2001, Specific immunoglobulin E responses in ZAP-70-deficient patients are mediated by Syk-dependent T-cell receptor signalling., Immunology., 103, 164, 10.1046/j.1365-2567.2001.01246.x · DOI
  15. Kipps, 2001, Chronic lymphocytic leukemia and related diseases. In Beutler E, Lichtman MA, Coller BS, Kipps TJ, Seligsohn U, eds. Williams Hematology., 1163
  16. Kipps, 1995, Flow cytometry., L56
  17. Rassenti, 1995, Analysis of immunoglobulin VH gene repertoire by an anchored PCR-ELISA., Ann N Y Acad Sci., 764, 463, 10.1111/j.1749-6632.1995.tb55866.x · DOI
  18. Corbett, 1997, Sequence of the human immunoglobulin diversity (D) segment locus: a systematic analysis provides no evidence for the use of DIR segments, inverted D segments, “minor” D segments or D-D recombination., J Mol Biol., 270, 587, 10.1006/jmbi.1997.1141 · DOI
  19. Kipps, 1989, Developmentally restricted VH gene expressed at high frequency in chronic lymphocytic leukemia., Proc Natl Acad Sci U S A., 86, 5913, 10.1073/pnas.86.15.5913 · DOI
  20. Howard, 1993, Formation and hydrolysis of cyclic ADP-ribose catalyzed by lymphocyte antigen CD38., Science., 262, 1056, 10.1126/science.8235624 · DOI
  21. Summerhill, 1993, Human lymphocyte antigen CD38 catalyzes the production of cyclic ADP-ribose., FEBS Lett., 335, 231, 10.1016/0014-5793(93)80735-D · DOI
  22. Mehta, 1996, Human CD38, a cell-surface protein with multiple functions., FASEB J., 10, 1408, 10.1096/fasebj.10.12.8903511 · DOI
  23. Lund, 1996, Signaling through CD38 augments B cell antigen receptor (BCR) responses and is dependent on BCR expression., J Immunol., 157, 1455, 10.4049/jimmunol.157.4.1455 · DOI
  24. Jelinek, 2001, Analysis of clonal B-cell CD38 and immunoglobulin variable region sequence status in relation to clinical outcome for B-chronic lymphocytic leukaemia., Br J Haematol., 115, 854, 10.1046/j.1365-2141.2001.03149.x · DOI
  25. Hamblin, 2000, Immunoglobulin V genes and CD38 expression in CLL., Blood., 95, 2455, 10.1182/blood.V95.7.2455 · DOI
  26. Hivroz, 1986, Heterogeneity of responsiveness of chronic lymphocytic leukemic B cells to B cell growth factor or interleukin 2., Eur J Immunol., 16, 1001, 10.1002/eji.1830160821 · DOI
  27. Hivroz, 1988, Cross-linking of membrane IgM on B CLL cells: dissociation between intracellular free Ca2+ mobilization and cell proliferation., Eur J Immunol., 18, 1811, 10.1002/eji.1830181124 · DOI
  28. Zupo, 1996, CD38 expression distinguishes two groups of B-cell chronic lymphocytic leukemias with different responses to anti-IgM antibodies and propensity to apoptosis., Blood., 88, 1365, 10.1182/blood.V88.4.1365.bloodjournal8841365 · DOI
  29. DeFranco, 1995, Transmembrane signaling by antigen receptors of B and T lymphocytes., Curr Opin Cell Biol., 7, 163, 10.1016/0955-0674(95)80024-7 · DOI
  30. Sefton, 1994, Role of tyrosine kinases in lymphocyte activation., Curr Opin Immunol., 6, 372, 10.1016/0952-7915(94)90115-5 · DOI
  31. Lankester, 1995, Antigen receptor nonresponsiveness in chronic lymphocytic leukemia B cells., Blood., 86, 1090, 10.1182/blood.V86.3.1090.1090 · DOI
  32. Semichon, 1997, Normal Syk protein level but abnormal tyrosine phosphorylation in B-CLL cells., Leukemia., 11, 1921, 10.1038/sj.leu.2400832 · DOI
  33. Latour, 1996, Differential intrinsic enzymatic activity of Syk and Zap-70 protein-tyrosine kinases., J Biol Chem., 271, 22782, 10.1074/jbc.271.37.22782 · DOI · Paper page
  34. Zoller, 1997, Protein tyrosine kinases Syk and ZAP-70 display distinct requirements for Src family kinases in immune response receptor signal transduction., J Immunol., 158, 1650, 10.4049/jimmunol.158.4.1650 · DOI · Paper page
  35. Ashe, 1999, ZAP-70 protein promotes tyrosine phosphorylation of T cell receptor signaling motifs (ITAMs) in immature CD4(+)8(+) thymocytes with limiting p56(lck)., J Exp Med., 189, 1163, 10.1084/jem.189.7.1163 · DOI · Paper page

Cited by

See all 426

Metadata

Authors
Chen, L., Widhopf, G., Huynh, L., Rassenti, L., Rai, K. R., Weiss, A., & Kipps, T. J.
Affiliations
From the Division of Hematology/Oncology, Department of Medicine, University of California, San Diego for the CLL Research Consortium, San Diego, CA; Long Island Jewish Hospital, New York, NY; and the Department of Medicine, Howard Hughes Medical Institute, University of California, San Francisco.
Venue
Blood
Publisher
American Society of Hematology
Published
2002-12-15
Volume
100
Issue
13
Pages
4609-4614
ISSN
  • 1528-0020
  • 0006-4971
DOI
10.1182/blood-2002-06-1683
Cited by
426
References
0
Language
en

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Expression of ZAP-70 is associated with increased B-cell receptor signaling in chronic lymphocytic leukemia. https://app.cochat.ai/papers/10.1182/blood-2002-06-1683
The paper
Chen, L., Widhopf, G., Huynh, L., Rassenti, L., Rai, K. R., Weiss, A., & Kipps, T. J. (2002). Expression of ZAP-70 is associated with increased B-cell receptor signaling in chronic lymphocytic leukemia. Blood. https://doi.org/10.1182/blood-2002-06-1683