CORRELATIONS BETWEEN THE CELLULAR AND MOLECULAR FEATURES OF THE DISEASE WITH THE CLINICAL COURSE OF B-CLL
How might features of the repertoire of IgVH genes used by B cells in B-CLL, the mutations status of these genes, and expression of molecules related to cellular activation and BCR signal transduction (CD38 and ZAP-70) be relevant to the clinical course of B-CLL? These disease manifests differently in different patients, depending on the utilization of mutated or unmutated IgVH genes and the expression of ZAP-70 and CD38 by the leukemic cells. One explanation is that activation via the BCR following recognition of (self) antigens activates the cells in vivo, accompanied by expression of CD38 and ZAP-70. Because the majority of U-CLL clones contain a self-reacting BCR, while most M-CLL clones do not, it is not unexpected that more activation markers are found on U-CLL cells. In addition, B-CLL clones from patients in different prognostics subsets differ in signaling capacity, with an intact BCR signal transductions pathway found most frequently among patients exhibiting unfavorable prognostic markers. Thus, continuous (auto)antigenic stimulation would likely represent a major factor for U-CLL cases and much less likely for M-CLL.
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