The clinical characteristics and prognosis in adult Ph negative acute lymphoblastic leukemia with TP53 aberrations

Abstract

Very few reports elucidate the prognosis of patients with TP53 aberrations using both measurable residual disease (MRD) and the status of having undergone allogeneic hematopoietic stem cell transplantation (allo-SCT). In this study, aberrations of TP53 were analyzed using next-generation sequencing (NGS) and fluorescence in situ hybridization (FISH) in patients with Philadelphia chromosome-negative (Ph−) ALL enrolled in a prospective single-arm clinical trial at our leukemia center. We analyzed the survival of the patients grouped according to the MRD level at the third month and whether or not received allo-SCT. We found that allo-SCT could improve the OS in patients with TP53 aberrations; Patients having negative MRD at the third month still showed worse 3-year OS and 3-year DFS without undergoing allo-SCT, which is different from previous studies, moreover, the prognostic significance of TP53 deletions was as important as TP53 mutations, the importance of screening both TP53 deletions and mutations in adult Ph− ALL at diagnosis should be emphasized.

TP53 deletion as an MRD-dependent risk factor in childhood B-ALL: a post hoc analysis from a prospective cohort

“…However, the impact of TP53 del on lymphoblastic leukemia is still unclear. Several domestic and foreign studies have found that TP53 del is associated with poor prognosis 7,11,12,19,22 . However, some studies have come to the opposite conclusion.…”

“…Previous studies have investigated the clinical features and prognostic significance of TP53 alterations, mostly TP53 mut alterations, in ALL patients 1,[8][9][10][11][17][18][19][20] . However, the clinical characteristics and prognostic impact of TP53 del in pediatric ALL at diagnosis has not been well-characterized due to limited research and large heterogeneity across studies.…”

“…TP53 aberrations, including mutations or deletions of the TP53 gene, can cause p53 inactivation and are found in approximately 50% of human cancers 1,9,11 . In hematological malignancies, the frequency of TP53 aberrations varies, with 16%-19% in ALL, which was associated with an inferior therapeutic response and lower survival rates in previous studies 1,9,11,12 . Due to large heterogeneity across studies, the prognostic significance of TP53 aberrations in pediatric ALL remains to be explored.…”

“…The transcription factor p53 is an essential regulator of various signaling pathways, including cell cycle arrest, apoptosis, DNA repair and genomic stability, and is known as a "genome guardian" 1,[8][9][10] . TP53 aberrations, including mutations or deletions of the TP53 gene, can cause p53 inactivation and are found in approximately 50% of human cancers 1,9,11 . In hematological malignancies, the frequency of TP53 aberrations varies, with 16%-19% in ALL, which was associated with an inferior therapeutic response and lower survival rates in previous studies 1,9,11,12 .…”

Influence of SPIO labelling on the function of BMSCs in chemokine receptors expression and chemotaxis

“…HCT is also a viable option for the relapse cases. Allo-HSCT has been successfully used to treat Philadelphia chromosome-negative acute lymphoblastic leukemia ( Chang et al, 2017 ; Xu et al, 2017 ; Zeng et al, 2021 ; Fan et al, 2019 ; Fang et al, 2022 ). However, it is beset with several challenges such as the lack of suitable donors ( Atilla, Ataca Atilla & Demirer, 2017 ; Zhu et al, 2018 ) and induction of acute graft-versus-host disease (aGVHD) ( Aladağ, Kelkitli & Göker, 2020 ; Naserian et al, 2020 ).…”