High iASPP (PPP1R13L) expression is an independent predictor of adverse clinical outcome in acute myeloid leukemia (AML).

Apoptosis-stimulating proteins of p53 (ASPPs) are a family of proteins that modulate key tumor suppressor pathways via direct interaction with p53. Deregulation of these proteins promotes cancer development and impairs sensitivity to systemic (chemo)therapy and radiation. In this study, we describe that the inhibitor of ASPP (iASPP) is frequently highly expressed in acute myeloid leukemia (AML) and that overexpression correlates with a poor clinical outcome.

Impact of TP53 Mutation Status in Elderly AML Patients When Adding All-Trans Retinoic Acid or Valproic Acid to Decitabine.

In a randomized phase II trial (AMLSG 14-09, NCT00867672) of elderly, newly diagnosed AML patients, ATRA combined with decitabine (DEC) significantly improved the overall response rate (ORR) and survival also in patients with adverse-risk genetics, without adding toxicity. We performed a post hoc analysis to determine the predictive impact of TP53 status. Despite a nominally higher ORR, the clinically meaningful survival benefit when adding ATRA to DEC was diminished, but not completely negated, in TP53-mutated patients.

Evaluation of apoptosis stimulating protein of TP53-1 (ASPP1/PPP1R13B) to predict therapy resistance and overall survival in acute myeloid leukemia (AML).

ASPP1 (PPP1R13B) belongs to a family of p53-binding proteins and enhances apoptosis by stimulation of p53-transactivation of selected proapoptotic target genes. It is preferentially expressed in hematopoietic stem cells (HSC) and together with p53 preserves the genomic integrity of the HSC pool. Consequently, dysfunction of ASPP1 has been associated with malignant transformation and development of acute lymphoblastic leukemias and lymphomas - whereas methylation of the promoter region is linked to reduced transcription and ultimately attenuated expression of ASPP1.

Treatment regimens in patients over 64 years with acute myeloid leukaemia: a retrospective single-institution, multi-site analysis.

Objectives: The aim of this study is to investigate the effect of treatment choice on survival, transfusion needs and hospitalizations in patients > 64 years old with newly diagnosed acute myeloid leukaemia (AML).

Material And Methods: This study retrospectively analysed patients over 64 years with AML diagnosed at a regional healthcare network in Switzerland between 2017 and 2020. Patients underwent four therapy groups: intensive chemotherapy (IC), hypomethylating agent in combination with the BCL2-Inhibitor venetoclax (HMA + VEN), hypomethylating agents alone (HMA) or best supportive care (BSC).