PMID- 22616724
OWN - NLM
STAT- MEDLINE
DCOM- 20130415
LR  - 20211203
IS  - 1029-2403 (Electronic)
IS  - 1042-8194 (Print)
IS  - 1026-8022 (Linking)
VI  - 53
IP  - 12
DP  - 2012 Dec
TI  - Targeting the B cell receptor pathway in chronic lymphocytic leukemia.
PG  - 2362-70
LID - 10.3109/10428194.2012.695781 [doi]
AB  - The B cell receptor (BCR) pathway plays a crucial role in the survival, 
      proliferation and trafficking of chronic lymphocytic leukemia (CLL) cells. 
      Inhibitors of the key kinases in this pathway, including spleen tyrosine kinase 
      (SYK), mammalian target of rapamycin (mTOR), phosphoinositide 3'-kinase (PI3K) 
      and Bruton's tyrosine kinase (BTK), have been found in preclinical models to 
      decrease CLL cell viability both directly and indirectly through modulation of 
      the microenvironment. Recently, oral agents targeting each of these kinases have 
      been explored in early phase clinical trials in patients with CLL. BCR pathway 
      antagonists appear to be highly active in relapsed/refractory CLL, independent of 
      high-risk disease markers such as del(17p). These agents have shown a unique 
      pattern of inducing early transient lymphocytosis, which typically is associated 
      with nodal response. Here, we review the biology of the BCR, the kinases within 
      this pathway and their interaction with the CLL microenvironment. We also discuss 
      data from recent and ongoing clinical trials of BCR antagonists. We address the 
      development of potential biomarkers for response to these agents such as ZAP-70, 
      IGHV status and CCL3, and discuss where these exciting new drugs may fit in the 
      evolving landscape of CLL therapy.
FAU - Davids, Matthew S
AU  - Davids MS
AD  - CLL Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 
      02215, USA.
FAU - Brown, Jennifer R
AU  - Brown JR
LA  - eng
GR  - T32 CA009172/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Leuk Lymphoma
JT  - Leukemia & lymphoma
JID - 9007422
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Receptors, Antigen, B-Cell)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (SYK protein, human)
RN  - EC 2.7.10.2 (Syk Kinase)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/antagonists & inhibitors/metabolism
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/*drug therapy/metabolism
MH  - Models, Biological
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Protein Kinase Inhibitors/*therapeutic use
MH  - Protein-Tyrosine Kinases/antagonists & inhibitors/metabolism
MH  - Receptors, Antigen, B-Cell/*metabolism
MH  - Signal Transduction/*drug effects
MH  - Syk Kinase
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/metabolism
PMC - PMC4557770
MID - NIHMS717235
EDAT- 2012/05/24 06:00
MHDA- 2013/04/16 06:00
PMCR- 2015/09/02
CRDT- 2012/05/24 06:00
PHST- 2012/05/24 06:00 [entrez]
PHST- 2012/05/24 06:00 [pubmed]
PHST- 2013/04/16 06:00 [medline]
PHST- 2015/09/02 00:00 [pmc-release]
AID - 10.3109/10428194.2012.695781 [doi]
PST - ppublish
SO  - Leuk Lymphoma. 2012 Dec;53(12):2362-70. doi: 10.3109/10428194.2012.695781.