Old and New Facts and Speculations on the Role of the B Cell Receptor in the Origin of Chronic Lymphocytic Leukemia.
chronic lymphocytic leukemia
immunoglobulin
ontogeny
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
17 Nov 2022
17 Nov 2022
Historique:
received:
20
10
2022
revised:
09
11
2022
accepted:
11
11
2022
entrez:
26
11
2022
pubmed:
27
11
2022
medline:
30
11
2022
Statut:
epublish
Résumé
The engagement of the B cell receptor (BcR) on the surface of leukemic cells represents a key event in chronic lymphocytic leukemia (CLL) since it can lead to the maintenance and expansion of the neoplastic clone. This notion was initially suggested by observations of the CLL BcR repertoire and of correlations existing between certain BcR features and the clinical outcomes of single patients. Based on these observations, tyrosine kinase inhibitors (TKIs), which block BcR signaling, have been introduced in therapy with the aim of inhibiting CLL cell clonal expansion and of controlling the disease. Indeed, the impressive results obtained with these compounds provided further proof of the role of BcR in CLL. In this article, the key steps that led to the determination of the role of BcR are reviewed, including the features of the CLL cell repertoire and the fine mechanisms causing BcR engagement and cell signaling. Furthermore, we discuss the biological effects of the engagement, which can lead to cell survival/proliferation or apoptosis depending on certain intrinsic cell characteristics and on signals that the micro-environment can deliver to the leukemic cells. In addition, consideration is given to alternative mechanisms promoting cell proliferation in the absence of BcR signaling, which can explain in part the incomplete effectiveness of TKI therapies. The role of the BcR in determining clonal evolution and disease progression is also described. Finally, we discuss possible models to explain the selection of a special BcR set during leukemogenesis. The BcR may deliver activation signals to the cells, which lead to their uncontrolled growth, with the possible collaboration of other still-undefined events which are capable of deregulating the normal physiological response of B cells to BcR-delivered stimuli.
Identifiants
pubmed: 36430731
pii: ijms232214249
doi: 10.3390/ijms232214249
pmc: PMC9693457
pii:
doi:
Substances chimiques
Receptors, Antigen, B-Cell
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
M.C. and G.C. have been supported by Gilead. The other authors declare no conflict of interest.
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