Diagnostic techniques and therapeutic challenges in patients withTP53dysfunctional chronic lymphocytic leukemia

Abstract

Aberrations of the TP53 pathway, whether by deletion or mutation, are increasingly recognized as one of the most important biological risk factors in chronic lymphocytic leukemia. Yet, there is little consensus on how to assess for TP53 defects in the clinic, and very few clinical studies to guide optimal management of such patients. In this review, we discuss the state-of-the-art in the assessment of the TP53 pathway, and review the evidence-base for therapeutic recommendations.

IL-17 induces radiation resistance of B lymphoma cells by suppressing p53 expression and thereby inhibiting irradiation-triggered apoptosis

“…An abnormality in p53 expression is involved in the pathogenesis of cancer. 9,10 Our data show that radiotherapy can upregulate the expression of p53 in k1106 cells, which is correlated with k1106 cell apoptosis after irradiation. Previous studies indicate that high levels of IL-17 are associated with the low levels of p53 in colorectal cancer.…”

“…The p53 protein is known as a tumor suppressor that operates by inducing tumor cell apoptosis and death. A number of reports have revealed p53 mutation or suppression in tumor cells, 9,10 which underscores the importance of the proper function of p53 in immune surveillance in the body. The factors that cause p53 abnormalities are unclear.…”

Long-term results of first salvage treatment in CLL patients treated initially with FCR (fludarabine, cyclophosphamide, rituximab)

“…Chemotherapy with purine-analog-containing regimens induces a TP53-dependent cellular response 4 and may contribute to the acquisition of (or selection for) a disease clone containing deletion and/or mutation of the TP53 gene. 5 However, the acquisition of a TP53 abnormality may not be the only important consideration in patients in who FCR therapy fails; there may be other clinical and biological variables that influence the outcome of subsequent treatment.…”

Treatment of Chronic Lymphocytic Leukemia with TP53 Aberrations

“…Delece krátkého raménka 17. chromozomu del(17p), zahrnující gen TP53 (v pruhu 17p13.1), představuje nejdůležitější prognostický faktor u chronické lymfocytární leukemie (CLL). Pa cienti s aberací TP53 progredují rychleji do symp tomatického onemocnění vyžadujícího léčbu, mají kratší trvání odpovědi na chemoimunoterapii a medián jejich celkové přežití (overall survival -OS) je kratší než tři roky od zahájení léčby [1][2][3]. Přítomnost této genetické abnormality řadí nemocné do skupiny tzv.…”