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

MARIA LAURA GABELLONI; BORGE MERCEDES; JEREMIAS GALLETI; CAÑONES CRISTIAN; PAULA FERNANDEZ CALOTTI; BEZARES RAIMUNDO FERNANDO; JULIO SANCHEZ AVALOS; MIRTA GIORDANO; GAMBERALE ROMINA

BRITISH JOURNAL OF HAEMATOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Año: 2008 vol. 140 p. 117 - 119

0007-1048

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.