Targeting p53 in chronic lymphocytic leukemia.

Introduction: Genomic studies have allowed to identify molecular predictors for chronic lymphocytic leukemia (CLL) treatment tailoring. disruption is the strongest predictor of chemo-refractoriness and its assessment is the first decisional node in the disease treatment algorithm.

Areas Covered: The review covers the p53 biological pathway, its genetic alterations and clinical implications in CLL, and its druggable targets.

An update on: molecular genetics of high-risk chronic lymphocytic leukemia.

: During the past few years, new genomic approaches have elucidated the molecular genetics of chronic lymphocytic leukemia (CLL) to a large extent. As a consequence, specific high-risk genetic features of the disease, e.g.

HIF-1α is over-expressed in leukemic cells from -disrupted patients and is a promising therapeutic target in chronic lymphocytic leukemia.

In chronic lymphocytic leukemia (CLL), the hypoxia-inducible factor 1 (HIF-1) regulates the response of tumor cells to hypoxia and their protective interactions with the leukemic microenvironment. In this study, we demonstrate that CLL cells from -disrupted ( ) patients have constitutively higher expression levels of the α-subunit of HIF-1 (HIF-1α) and increased HIF-1 transcriptional activity compared to the wild-type counterpart. In the subset, HIF-1α upregulation is due to reduced expression of the HIF-1α ubiquitin ligase von Hippel-Lindau protein (pVHL).

Potential of BCL2 as a target for chronic lymphocytic leukemia treatment.

Chronic lymphocytic leukemia (CLL) is a highly heterogeneous disease. Deregulation of apoptosis is a major pathogenetic feature, and represents a therapeutic target. TP53 disrupted patients are categorized as high risk patients and are treated with novel target therapies.