TY - JOUR
T1 - Immunogenetic studies of chronic lymphocytic leukemia
T2 - Revelations and speculations about ontogeny and clinical evolution
AU - Vardi, Anna
AU - Agathangelidis, Andreas
AU - Sutton, Lesley Ann
AU - Ghia, Paolo
AU - Rosenquist, Richard
AU - Stamatopoulos, Kostas
PY - 2014/8/15
Y1 - 2014/8/15
N2 - Over the last decade, immunogenetic analysis of B-cell receptor immunoglobulins (BcR IG) has proved instrumental in dissecting chronic lymphocytic leukemia (CLL) pathogenesis. Initially, it was the finding that the level of somatic hypermutations in rearranged IG heavy-chain genes could define two CLL subtypes associated with a different clinical course that drew attention. As the years ensued, this not only continued to hold strong, but also revealed an unprecedented BcR restriction (aptly coined as " stereotypy"), thus cementing the idea that antigenic elements select the leukemic clones. With all this in mind, in the present review, we focus on the CLL BcR IG, a molecule that clearly lies at the heart of disease pathogenesis, and attempt to distil from past and emerging biologic knowledge the most relevant aspects in the context of the immunogenetics of CLL, while at the same time provoking questions that remain unanswered. We juxtapose CLL with mutated BcR IGs against CLL with unmutated BcR IGs due to their striking clinicobiologic differences; however, when considering ontogeny, common derivation of the two mutational subtypes cannot be excluded. The issue of stereotypy is intertwined throughout and we also raise the subject of isotype-switched CLL, which, despite its rarity, contributes intriguing ontogenetic hints.
AB - Over the last decade, immunogenetic analysis of B-cell receptor immunoglobulins (BcR IG) has proved instrumental in dissecting chronic lymphocytic leukemia (CLL) pathogenesis. Initially, it was the finding that the level of somatic hypermutations in rearranged IG heavy-chain genes could define two CLL subtypes associated with a different clinical course that drew attention. As the years ensued, this not only continued to hold strong, but also revealed an unprecedented BcR restriction (aptly coined as " stereotypy"), thus cementing the idea that antigenic elements select the leukemic clones. With all this in mind, in the present review, we focus on the CLL BcR IG, a molecule that clearly lies at the heart of disease pathogenesis, and attempt to distil from past and emerging biologic knowledge the most relevant aspects in the context of the immunogenetics of CLL, while at the same time provoking questions that remain unanswered. We juxtapose CLL with mutated BcR IGs against CLL with unmutated BcR IGs due to their striking clinicobiologic differences; however, when considering ontogeny, common derivation of the two mutational subtypes cannot be excluded. The issue of stereotypy is intertwined throughout and we also raise the subject of isotype-switched CLL, which, despite its rarity, contributes intriguing ontogenetic hints.
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UR - http://www.scopus.com/inward/citedby.url?scp=84905980544&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-14-0630
DO - 10.1158/0008-5472.CAN-14-0630
M3 - Article
C2 - 25074616
AN - SCOPUS:84905980544
VL - 74
SP - 4211
EP - 4216
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 16
ER -