CXCL12-induced chemotaxis is impaired in T cells from ZAP-70- chronic lymphocytic leukemia patients.

BORGE MERCEDES; NANNINI PAULA ROMINA; GALLETTI JEREMÍAS; MORANDE PABLO; JULIO SANCHEZ AVALOS; BEZARES RAIMUNDO FERNANDO; GIORDANO MIRTA; GAMBERALE ROMINA

HAEMATOLOGICA

FERRATA STORTI FOUNDATION

Lugar: Pavia, Italia; Año: 2010 p. 768 - 775

0390-6078

BackgroundT cells from patients with chronic lymphocytic leukemia may play an important role in contributingto the onset, sustenance, and exacerbation of the disease by providing survival andproliferative signals to the leukemic clone within lymph nodes and bone marrow.Design and MethodsBy performing chemotaxis assays towards CXCL12, CCL21 and CCL19, we sought to evaluatethe migratory potential of T cells from chronic lymphocytic leukemia patients. We nextanalyzed the chemokine-induced migration of T cells, dividing the chronic lymphocyticleukemia samples according to their expression of the poor prognostic factors CD38 and ZAP-70 in leukemic cells determined by flow cytometry.ResultsWe found that T cells from patients with chronic lymphocytic leukemia are less responsive toCXCL12, CCL21 and CCL19 than T cells from healthy adults despite similar CXCR4 andCCR7 expression. Following separation of the patients into two groups according to ZAP-70expression, we found that T cells from ZAP-70-negative samples showed significantly lessmigration towards CXCL12 compared to T cells from ZAP-70-positive samples and that thiswas not due to defective CXCR4 down-regulation, F-actin polymerization or to a lesser expressionof ZAP-70, CD3, CD45, CD38 or CXCR7 on these cells. Interestingly, we found thatleukemic cells from ZAP-70-negative samples seem to be responsible for the defective CXCR4migratory response observed in their T cells.ConclusionsImpaired migration towards CXCL12 may reduce the access of T cells from ZAP-70-negativepatients to lymphoid organs, creating a less favorable microenvironment for leukemic cell survivaland proliferation