| Autor: |
Richardson SJ; Department of Haematology Level 7, Derriford Hospital, Plymouth PL6 8DH, United Kingdom. sarah.richardson@phnt.swest.nhs.uk, Matthews C, Catherwood MA, Alexander HD, Carey BS, Farrugia J, Gardiner A, Mould S, Oscier D, Copplestone JA, Prentice AG |
| Jazyk: |
angličtina |
| Zdroj: |
Blood [Blood] 2006 May 01; Vol. 107 (9), pp. 3584-92. Date of Electronic Publication: 2005 Dec 06. |
| DOI: |
10.1182/blood-2005-04-1718 |
| Abstrakt: |
Molecular markers like IgV(H) mutational status, chromosomal abnormalities, and CD38 and ZAP-70 expression have prognostic value in B-cell chronic lymphocytic leukemia (B-CLL). These may be pathogenetic because of the coincidental expression of ZAP-70 and increased B-cell receptor (BCR) signaling and the signaling function of CD38 in CLL. This study shows that ZAP-70(+) CLL B cells respond in vitro more readily than ZAP-70(-) CLL and normal B cells to chemokine migratory signals through enhanced surface CCR7 expression (P = .009; P < .001) and increased responsiveness to its ligands CCL19 and CCL21, demonstrated by F-actin polymerization (P < .05) and cellular migration (P < .01). In addition, ZAP-70(+) CLL cells exhibit sustained ERK phosphorylation/activation following stimulation with CXCL12 (SDF1-alpha, a survival factor produced by stromal cells) compared with ZAP-70(-) cells (P = .004). Following coculture with nurse-like cells, the survival of ZAP-70(+) but not ZAP-70(-) CLL cells is significantly enhanced by the addition of CXCL12 (P < .05), an effect that is partially blocked by the MEK inhibitor PD98059. These advantageous migratory and survival responses may promote easier access to and greater proliferation in pseudo-germinal centers and explain in part the more progressive nature of ZAP-70(+) disease. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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