B-cell malignancies represent a diverse collection of neoplasms.
B-cell malignancies may occur due to dysregulation of normal development and maturation processes.
Many different subtypes of B-cell malignancies, which are divided into Hodgkin’s lymphomas and non-Hodgkin’s lymphomas.
B-cell lymphomas are heterogeneous and can vary from being aggressive to relatively indolent.
Include: Mantle cell lymphoma. follicular lymphoma, diffuse large B-cell lymphoma, CLL, Hodgkin lymphoma and marginal zone lymphoma.
The tumor micro environment has an impact on the course of disease and includes stromal cells, T-cells, soluble factors and other nodal and bone marrow cells.
Tumor microenvironment can effect B-cell malignancies effecting apoptosis, proliferation, migration and adhesion.
The tumor micro environment influences B-cell development and growth.
B-cell lymphomas associated with increased risk include: occupational and environmental exposure to certain pesticides and herbicide, immunosuppression associated with HIV, auto immune disorders, iatrogenic induced immune suppression in the post transplant in other settings, family history, and a personal history of a prior cancer, including Hodgkin’s lymphoma and prior NHL.
The intracellular protein kinases are essential components of the B-cell receptor (BCR), chemokine receptors, and other signaling pathways, and have a broad effect on many types of signaling.
B cell receptor activates multiple signaling pathways in B-cells necessary for thie immune response.
In B-cell malignancies inappropriately activate some signaling pathways, such as the BCR.
Bruton’s tyrosine kinase (BTK), Lyn (an Src family tyrosine-protein kinase), phosphoinositide 3 kinase (PI3K), protein kinase C (PKC)-β, spleen tyrosine kinase (SYK), and other kinases are part of signaling cascades that drive uncontrolled proliferation and survival of malignant B cells.
Kinases including Bruton’s tyrosine kinase (BTK), Lyn (an Src family tyrosine-protein kinase), phosphoinositide 3 kinase (PI3K), protein kinase C (PKC)-β, and spleen tyrosine kinase (SYK) are part signaling cascades that drive uncontrolled proliferation and survival of malignant B cells.
Malignant B cells often express factors on the cell surface that need promote homing to proliferative environments.
Bruton’s tyrosine kinase (BTK) has a key role in B-cell homing.
Intracellular protein kinases are therapeutic targets for the treatment of certain B-cell malignancies.