SHIP-1 protein level and phosphorylation status differs between CLL cells segregated by ZAP-70 expression

GABELLONI L; BORGE M; GALLETTI J; CAÑONES C; NANNINI P; MORANDE P; BEZARES RF; GIORDANO M; GAMBERALE R

Londres, UK

Workshop; XII International Workshop on CLL.; 2007

<!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:ES; mso-fareast-language:ES;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> Leukemic cells from aggressive CLL patients typically express the protein tyrosine kinase ZAP-70 and display a more effective BCR signal transduction that could contribute to their relatively aggressive clinical behavior compared to ZAP-70- patients.  When both groups of patients were evaluated for the expression of the inhibitory phosphatase SHIP-1, which can counterbalance BCR activation, we found that ZAP-70- CLL cells not only displayed a higher SHIP-1 protein expression compared to ZAP-70+ subgroup, but also it was constitutively tyrosine phosphorylated to a greater extent. We also found that, in ZAP-70- but not in ZAP-70+ patients, BCR cross-linking increases SHIP-1 phosphorylation status suggesting that it exclusively participates in BCR signal transduction in the former subgroup of patients. Given that SHIP-1 can negatively modulate not only BCR but also cytokine and chemokine receptor signaling, the possibility exists that ZAP-70- CLL cells, by expressing higher SHIP-1 levels, hold higher signaling thresholds to different microenvironment stimuli.