Details

Autor(en) / Beteiligte

• Muggen, A.F
• Pillai, S.Y
• Kil, L.P
• van Zelm, M.C
• van Dongen, J.J.M
• Hendriks, R.W
• Langerak, A.W

Titel

Basal [Ca.sup.2+] signaling is particularly increased in mutated chronic lymphocytic leukemia

Ist Teil von

• Leukemia, 2015-02, p.321

Ort / Verlag

Nature Publishing Group

Erscheinungsjahr

2015

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• On the basis of somatic hypermutation status of their B-cell antigen receptor (BCR) genes, chronic lymphocytic leukemia (CLL) patients can be divided into unmutated CLL (U-CLL) or mutated CLL (M-CLL). Approximately 30% of CLL patients express a stereotypic BCR, which may indicate that specific antigenic stimulation is driving CLL pathogenesis. Recently, it was reported that BCRs from CLL cells are capable of antigen-independent, cell-autonomous signaling, through recognition of an internal framework 2 (FR2) BCR epitope. We hypothesized that the level of cell-autonomous signaling may differ between CLL subgroups. Therefore, we analyzed [Ca.sup.2+] signaling in a series of primary stereotypic or heterogeneous U-CLL and M-CLL (n = 68) and healthy controls (n = 14). We confirmed that basal [Ca.sup.2+] signaling in CLL cells is higher than in normal B cells. Interestingly, we found that basal signaling was particularly increased in M-CLL. The degree of basal signaling did not correlate with membrane immunoglobulin levels, HCDR3 characteristics or FR2/FR3 sequence. We conclude that the level of basal [Ca.sup.2+] signaling is not uniformly enhanced in CLL B cells, but is associated with CLL immunoglobulin heavy chain V mutational status, reflecting a distinct cellular origin and possibly a different anergic state induced by repetitive or continuous antigen binding in vivo. Leukemia (2015) 29, 321-328; doi: 10.1038/leu.2014.188