AI Article Synopsis
- ZAP70 plays a significant role in chronic lymphocytic leukemia (CLL) by affecting B-cell receptor signaling, which is crucial for the disease's development.
- Research shows that a notable number of nonmalignant B cells in CLL patients express ZAP70, which is not the case for healthy individuals, indicating a potential early marker of disease progression.
- The presence of these ZAP70+ normal B cells is linked to autoimmune cytopenia, suggesting that they might contribute to autoimmune complications associated with CLL through autoreactive antibodies.
Article Abstract
ZAP70 has a prognostic value in chronic lymphocytic leukemia (CLL), through altered B-cell receptor signaling, which is important in CLL pathogenesis. A good correlation between ZAP70 expression in CLL cells and the occurrence of autoimmune phenomena has been reported. Yet, the great majority of CLL-associated autoimmune cytopenia is due to polyclonal immunoglobulin (Ig) G synthesized by nonmalignant B cells, and this phenomenon is poorly understood. Here, we show, using flow cytometry, that a substantial percentage of CD5- nonmalignant B cells from CLL patients expresses ZAP70 compared with CD5- B cells from healthy subjects. This ZAP70 expression in normal B cells from CLL patients was also evidenced by the detection of ZAP70 mRNA at single-cell level with polyclonal Ig heavy- and light-chain gene transcripts. ZAP70+ normal B cells belong to various B-cell subsets and their presence in the naïve B-cell subset suggests that ZAP70 expression may occur during early B-cell development in CLL patients and potentially before malignant transformation. The presence of ZAP70+ normal B cells is associated with autoimmune cytopenia in CLL patients in our cohort of patients, and recombinant antibodies produced from these ZAP70+ nonmalignant B cells were frequently autoreactive including anti-platelet reactivity. These results provide a better understanding of the implication of ZAP70 in CLL leukemogenesis and the mechanisms of autoimmune complications of CLL.
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| http://dx.doi.org/10.1002/ajh.27137 | DOI Listing |
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