Signaling molecules and cytokine production in T cells of patients with B-cell chronic lymphocytic leukemia: long-term effects of fludarabine and alemtuzumab treatment.

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BlankSignaling molecules and cytokine production in T cells of patients with

B-cell chronic lymphocytic leukemia: long-term effects of fludarabine and

alemtuzumab treatment.

S Kiaii, A Choudhury, F Mozaffari, R Rezvany, J Lundin, H Mellstedt, and A

Osterborg

Leuk Lymphoma, July 1, 2006; 47(7): 1229-38.

Immune and Gene Therapy Laboratory, Cancer Center Karolinska.

Fludarabine and alemtuzumab are routinely used for treatment of B-cell

chronic lymphocytic leukemia (B-CLL). The present study aimed to compare the

expression of signaling molecules and cytokine production by T cells of B-CLL

patients in long-term unmaintained remission/plateau phase following fludarabine

or alemtuzumab treatment with that of indolent/untreated B-CLL patients and

healthy donors. The frequency and intensity of TCR-CD3zeta chain, p56lck,

p59fyn, ZAP-70, PI3-kinase and interferon (IFN)-gamma/interleukin (IL)-4

production in CD4 and CD8 T cells was examined by flow cytometry. T-cell

function was assessed by stimulation with purified protein derivative (PPD) and

phytohemagglutinin (PHA). Despite a reduction in number, the expression of

IFN-gamma/IL-4 in T-cells in patients was significantly higher than in healthy

donors. The intensity of most signaling molecules in treated patients was

relatively unaffected vs. healthy donors but lower than untreated-indolent

patients. However, the total number of T cells which expressed each of the

signaling molecules was decreased in patients, with no difference between

fludarabine- and alemtuzumab-treated patients. The T-cell response to PHA but

not PPD was reduced in treated patients. The results suggest that, despite some

alterations in signaling molecules and a reduction in T-cell number, overall

T-cell functions may be relatively well preserved long-term after treatment with

fludarabine and alemtuzumab.

Publication Type:

a.. Journal article

PMID: 16923551