Response to azacitidine is independent of p53 expression in higher-risk myelodysplastic syndromes and secondary acute myeloid leukemia

p53 protein expression in patients with myelodysplasia treated with allogeneic bone marrow transplantation

“…An association has been reported between intense p53 nuclear staining and TP53 mutation in MDS (11,13,17); furthermore, patients without TP53 mutations did not exhibit intense p53 protein staining, conferring a good negative predictive value for IHC (12). Therefore, the acceptable sensitivity of p53 immunostaining in predicting for TP53 mutations is encouraging, and the methodology is routine in diagnostic laboratories.…”

“…It has been previously demonstrated that aberrant nuclear expression of p53 protein is associated with hemizygous p53 deletion in multiple myeloma (8,9) and chronic lymphocytic leukemia (10). In MDS, immunohistochemical staining for TP53 protein in bone marrow trephine biopsies has revealed a strong correlation with TP53 mutation status (11)(12)(13).…”

New therapeutic approaches in myelodysplastic syndromes: Hypomethylating agents and lenalidomide

“…In vitro data suggest that HMA-induced cell death may be P53-independent 71 , and in vivo experiments support the notion that HMA-induced differentiation is also P53-independent 58 . The latter can be reconciled with the finding that response rates to HMA appear independent of TP53 status or expression 72,73 . However, the survival of TP53 patients remains poor under HMA 72,73 , and there is no direct evidence from randomized trials that the poor prognosis of TP53 is even partly alleviated by HMA.…”

Preparing Patients With Myelodysplastic Syndrome for Transplant When Is Pre-transplant Cytoreductive Therapy Appropriate?

“…From a molecular perspective, it seems reasonable to propose this approach to MDS patients with DNMT3A and TET2 mutations because these aberrations have on the one hand been associated with relative resistance to chemotherapy [20,21] and on the other hand with an increased sensitivity towards HMA [28,29]. Interestingly, the response to HMA does not seem to be impaired in patients with TP53 mutations, although the long-term outcome on HMA alone in this subset is poor [30,31]. Thus, one or two cycles of HMA might be a reasonable approach to reduce leukemic burden in TP53-mutated MDS.…”