GENETIC ISSUES IN LYMPHOPROLIFERATIVE DISORDERS, ASPECTS OF GENETIC  BASED PATHOPHYSIOLOGY IN THIS DISEASE

Now it is established that lymphoma are due to a critical event causing Heavy chain IgH to be transposed into proximity with a promoter of PAX5 gene leading to 2 events
1. stimulation of TLE4 that force differentiation to lymphocyte proliferation. TLE4 is a tranduction enhancer which tell the cell no Brain differentiation by a negative regulation of the Groucho family members!  but it does force proliferation of lymphoblasts forward.

2.to insure survival of lymphoblasts, it consumes or de-repress the Death protein 6 leaving FAS intact and therefore NO APOPTOSIS, and favoring an intact Kinechore plate to preserve speedy cell division by preserving the Centromere  protein C.  Decrease of the Death receptor has a significant  3rd effect on a series of TNF receptors and ligand which ultimately through ETS1 and TTRAP end up affecting CD40 leading to weakening of the cell presentation of Antigen which is the underlying immunodeficeinec in lymphoma (similar to hyper IgM Syndrome)

This is the underlying pathophysiology of Lymphoma as it looks today.

OF NOTE CD40 IS ALSO INVOLVED IN ALZHEIMER!
JUST REMEMBER THE CD40 THRU TRAF GENES INTERACTS WITH CD30 TO ACTIVATE THE NF-kB AND CYCLINS!

CRITICAL TARGET IN THIS PATHWAYS

1.PROTEIN QD
2,KINETOCHORE, CENTROMERE PROTEIN C
3.FAS
4.DEATH PROTEIN 6
5.TTRAP
6.CD40
7.CD30
8.TRAF (s)
9.CASPASE 8
10.TNF