Association of Minimal Residual Disease With Superior Survival Outcomes in Patients With Multiple Myeloma: A Meta-analysis.

Importance: Numerous studies have evaluated the prognostic value of minimal residual disease (MRD) in patients with multiple myeloma (MM). Most studies were small and varied in terms of patient population, treatment, and MRD assessment methods.

Objective: To evaluate the utility of MRD detection in patients with newly diagnosed MM.

The gene expression signature associated with TP53 mutation/deletion in chronic lymphocytic leukaemia is dominated by the under-expression of TP53 and other genes on chromosome 17p.

In chronic lymphocytic leukaemia (CLL), TP53 mutation and deletion are strongly associated with one another and with adverse clinical outcome. Mutant TP53 protein typically accumulates to high levels and has been reported to have transcriptional regulatory activity distinct from that of wild-type TP53. To investigate whether such an effect is relevant to CLL, carefully balanced primary CLL samples with or without TP53 mutation/deletion were compared for their gene expression profiles using high-density DNA microarrays.

A novel type of p53 pathway dysfunction in chronic lymphocytic leukemia resulting from two interacting single nucleotide polymorphisms within the p21 gene.

The ATM-p53 pathway plays an important role in the biology of chronic lymphocytic leukemia (CLL). Its functional integrity can be probed by exposing CLL cells to ionizing radiation (IR) and measuring levels of p53 protein and one of its transcriptional targets, the cyclin-dependent kinase inhibitor p21. We have previously identified two abnormal p53/p21 response patterns associated with inactivating mutations of TP53 and ATM, respectively.

Hsp90 inhibition has opposing effects on wild-type and mutant p53 and induces p21 expression and cytotoxicity irrespective of p53/ATM status in chronic lymphocytic leukaemia cells.

In chronic lymphocytic leukaemia (CLL), mutation/deletion of TP53 is strongly associated with early disease progression, resistance to chemotherapy and short patient survival. Consequently, there is a pressing need to develop novel treatment protocols for this high-risk patient group. The present study was performed to evaluate Hsp90 inhibition as a possible therapeutic approach for such patients.