TP53-altered higher-risk myelodysplastic syndromes/neoplasms and acute myeloid leukemia: a distinct genetic entity with unique unmet needs

被引:2
|
作者
Ball, Somedeb [1 ]
Loghavi, Sanam [2 ]
Zeidan, Amer M. [3 ]
机构
[1] Univ S Florida, Div Hematol & Med Oncol, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33620 USA
[2] MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX USA
[3] Yale Canc Ctr, Dept Internal Med, Sect Hematol, New Haven, CT 06510 USA
关键词
p53; AML; MDS; myeloid malignancy; WHO; 2022; ICC; HEALTH-ORGANIZATION CLASSIFICATION; TP53; MUTATIONS; MUTANT P53; AZACITIDINE; OUTCOMES; CORRELATE; IMPACT; ABNORMALITIES; DECITABINE; VENETOCLAX;
D O I
10.1080/10428194.2022.2136969
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Pathogenic alterations of TP53 are an independent poor prognostic factor in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Clinical course of TP53- altered myeloid neoplasms is dictated by genetic characteristics, such as TP53 allelic state and variant allele frequency (VAF), and not the blast count. Hence, it was recently proposed that MDS (with increased blasts) and AML with TP53 alterations may be best classified as a single molecular disease entity, TP53-mutated higher-risk (HR)-MDS/AML. TP53 mutations drive resistance to intensive chemotherapies and less intensive hypomethylating agents (HMA). Novel combinations incorporating BCL2 inhibitor venetoclax improve response rates for TP53-mutated subgroup, but the survival is not improved. Early clinical studies combining HMA with investigational agents demonstrated activity in TP53-mutated HR-MDS/AML, but updated results with larger samples, longer follow-up, or randomized trials were less impressive to date. Future research should focus on finding novel, potentially disease-modifying therapies to improve outcomes in patients with TP53-mutated HR-MDS/AML.
引用
收藏
页码:540 / 550
页数:11
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