Blood, 1 February 2003, Vol. 101, No. 3, pp. 788-788
Antigen receptor signaling in CLL
is the line
dead?
B-cell chronic lymphocytic leukemia (CLL) can be
segregated into 2 subtypes based upon the nature of the expressed
immunoglobulin (Ig) genes. Leukemia cells that use unmutated Ig
more often express CD38 and are associated with a higher tendency
toward disease progression than are CLL cells that express mutated Ig.
Lanham and colleagues (page 1087) presents evidence that CLL cells that have unmutated Ig are more likely than CLL cells with mutated Ig to
undergo tyrosine phosphorylation of cytosolic proteins (a mark of
signal transduction) upon ligation of the B-cell receptor (BCR) for
antigen. These observations are in agreement with those of others (Chen
et al, Blood. 2002;100:4609-4614) and suggest that the 2 subtypes of
leukemia differ in their capacity to respond to the crosslinking
of their surface Ig by antigen. Not unexpectedly, the association
between mutational status and signal transduction capacity
was not absolute but probably reflects other biologic differences
between the 2 leukemia subtypes.
One likely candidate for this is ZAP-70, a protein tyrosine
kinase required for receptor signaling in T cells that often is expressed by CLL cells with unmutated Ig, but generally not by CLL with
mutated Ig or normal B cells (Rosenwald et al, J Exp Med.
2001;194:1639-1647). The study of Chen et al found that the capacity to
signal via the BCR for antigen was associated most closely with the
expression of this kinase, even in unusual cases that expressed ZAP-70
but used mutated Ig receptors. Conceivably, the difference in the
capacity of the leukemia cells to be stimulated by ligation of their
BCR relates to differences in the noted clinical behavior of these 2 subtypes of CLL. If so, then analyses of the receptor signaling
capacity might provide for a more reliable prognostic indicator than
expression of CD38, Ig mutational status, or other features found
differentially expressed by the 2 subtypes of this leukemia.
Thomas J. Kipps
University of California at San Diego
