P53 (TP53) Deletion
Although previously difficult to detect, the advent of FISH analysis of interphase cells from patients with B-CLL showed that around 17% of patients with the disease have deletions of the P53 (TP53) gene1. As with ATM, deletions of P53 have important therapeutic implications for patients with B-CLL2.
Knowledge of the P53 deletion status in the patient should mediate the choice of therapy3. P53 is a tumour suppressor gene and its protein product is responsible for the death of cells that contain damaged DNA. This is thought to be brought about by phosphorylation of P53 and the subsequent prevention of its repression by MDM2 (Mouse Double Minute 2 Homolog). This phosphorylation is mediated by ATM. In the absence of P53 activity, cells that cannot be repaired by ATM will continue to proliferate in their damaged state. Patients deleted for P53 may be rendered resistant to alkylating chemotherapeutic agents3 and purine analogues4 as these are designed to damage DNA in the cells that P53 would have destroyed. In the absence of P53, therefore, patients treated with these agents will harbour a proliferating population of damaged cells.
1. Döhner et al., J Mol Med 1999;77:266-81
2. Foá et al., Haematol 2013; 98(5):675-685
3. Sturm et al., Cell Death Differ. 2003 Apr;10(4):477-84
4. Döhner et al., Blood. 1995 Mar 15;85(6):1580-9
- Area of Interest*
- ALL, AML, CLL, Lymphoma, MDS, MM
This product is intended to be used on Carnoy’s solution (3:1 methanol/acetic acid) fixed haematological samples, or formalin-fixed paraffin-embedded (FFPE) tissues.
*Disease information supported by the literature and is not a reflection of the intended purpose of this product.