The Response to Surface IgM and IgD Cross-Linking Defines Different Groups of B-CLL.

The present study investigated the response of 184 B-CLLs cases to surface IgM or IgD cross-linking. Three groups of B-CLL cells were defined by the response to IgM stimulation. In 101 cases, the cells responded by undergoing apoptosis; in 8 cases, spontaneous apoptosis was inhibited and in 75 cases no response was observed. Statistical correlation was found between CD38 expression and apoptosis induction. Surface IgD cross-linking defined three groups of B-CLL. In 74 cases, spontaneous apoptosis was inhibited, in 12 cases, apoptosis was increased and in 98 cases no response was recorded. No statistical correlations was found between prognostic marker and response to surface IgD.When the responses to IgM and IgD cross-linking were analyzed together, the following B-CLL groups were found: A) B-CLLs responding to IgD by inhibition of apoptosis and not responding to IgM (14%), were CD38-negative (81%), VH genes mutated (76%), and ZAP-70 negative (84%); B) B-CLLs responding to IgD by inhibition of apoptosis and to IgM by apoptosis induction (23%), were VH genes unmutated (73%) and ZAP-70 strong (54%) while 50% of cases were CD38 positive.C) B-CLLs not responding to IgD but responding to IgM cross-linking by apoptosis induction (27%), were mainly CD38-negative (65%) VH genes mutated (69%) and ZAP-70 negative (78%).D) B-CLLs not responding to both stimuli (26%) in which there was an equal distribution of CD38 and ZAP-70-positive or negative cases, but were predominantly VH genes unmutated (63%).The distribution pattern of the prognostic markers in above groups was statistically significant. The cases also differed in their clinical outcome.Group A cases had a statistically significant longer treatment free survival (153 months) as compared to group B (36 months), group C (46 months) and group D (13 months, p=0.04). These data indicate that response to surface Ig stimulation may influence the progression of disease and can be taken as a further factor for determining the prognosis.