Normal B cells express ZAP70 in chronic lymphocytic leukemia: A link between autoimmunity and lymphoproliferation?
Fiche publication
Date publication
octobre 2023
Journal
American journal of hematology
Auteurs
Membres identifiés du Cancéropôle Est :
Pr HERBRECHT Raoul, Dr VALLAT Laurent, Pr MARTIN Thierry, Dr DRENOU Bernard
Tous les auteurs :
Ghergus D, Martin M, Knapp AM, Delmotte F, Joublin-Delavat A, Jung S, Schickel JN, Mendel I, Dupuis A, Drénou B, Ghesquières H, Salles G, Baseggio L, Herbrecht R, Korganow AS, Vallat L, Soulas-Sprauel P, Meffre E, Martin T
Lien Pubmed
Résumé
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.
Référence
Am J Hematol. 2023 10 19;: