Clinical outcomes and characteristics of patients with TP53-mutated myelodysplastic syndromes

Lijuan Zhang; Kankan Chen; Yingying Li; Qiuni Chen; Wenting Shi; Tingting Ji; Hong Tao; Zhengmei He; Chunling Wang; Liang Yu

doi:10.1080/16078454.2023.2181773

Clinical outcomes and characteristics of patients with TP53-mutated myelodysplastic syndromes

Hematology. 2023 Dec;28(1):2181773. doi: 10.1080/16078454.2023.2181773.

Authors

Lijuan Zhang^{1

2

3}, Kankan Chen^{1

2

3}, Yingying Li^{1

2

3}, Qiuni Chen^{1

2

3}, Wenting Shi^{1

2

3}, Tingting Ji^{1

2

3}, Hong Tao^{1

2

3}, Zhengmei He^{1

2

3}, Chunling Wang^{1

2

3}, Liang Yu^{1

2

3}

Affiliations

¹ Department of Hematology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, People's Republic of China.
² Department of Hematology, The Huai'an Clinical College of Xuzhou Medical University, Huai'an, People's Republic of China.
³ Key Laboratory of Hematology of Nanjing Medical University, Nanjing, People's Republic of China.

PMID: 36892252
DOI: 10.1080/16078454.2023.2181773

Abstract

Objective: To explore the clinical outcomes and characteristics of TP53-mutated primary myelodysplastic syndromes (MDS).

Methods: A total of 74 de novo primary MDS patients who were diagnosed and treated in the Department of Hematology of our hospital from January 2018 and September 2021 were analyzed retrospectively. All patients had evaluable blood cell counts, mean corpuscular volume (MCV), lactate dehydrogenase (LDH), bone marrow (BM) morphology, biopsy, and MDS-related 20-gene mutations sequencing. In addition, 69 of 74 patients had complete cytogenetic analysis through conventional chromosome analysis and fluorescence in-situ hybridization.

Results: Patients were divided into two cohorts, the TP53-mutated type (TP53^Mut) group (n = 19) and TP53 wild type (TP53^WT) group (n = 55). Compared with the TP53^WT group, patients in the TP53^Mut group had higher ratios of cytogenetic abnormalities (82.4% vs. 30.8%, P < 0.001), with 5q- karyotype (64.70% vs. 38.5%, P < 0.001), complex karyotype(CK) (64.70% vs. 38.5%, P < 0.001), HR-MDS (94.7% vs. 61.8%, P = 0.008), and acute myelogenous leukemia (AML) transformation (26.3% vs. 12.7%, P < 0.001). Interestingly, patients in the TP53^Mut group had lower median MCV than the TP53^WT group (94.40 fl vs. 101.90 fl, P = 0.008). Furthermore, MCV = 100 fl as cutoff, and found that MCV ≤ 100 fl was more common in the TP53^Mut group (73.7% vs. 38.2%, P < 0.001). After 1-4 courses of HMA ± chemotherapy, the overall response rate of the TP53^Mut group was higher than the TP53^WT group (83.3% vs. 71.4%, P = 0.012). With the median follow-up 12.0 months (1-46 months), the results show that the median OS and leukemia-free survival (LFS) of TP53^Mut group was significantly shorter than the TP53^WT group (P = 0.0018; P = 0.0310). Results of multivariate Cox proportional hazard analyses show TP53 mutation was an independent prognostic factor for the OS (HR 2.724, 95%CI 1.099-6.750, P = 0.030).

Conclusion: TP53-mutated primary MDS patients were associated with higher frequency of cytogenetic abnormalities, with 5q- karyotype, CK, AML transformation, higher risk IPSS-R, lower MCV and sensitive to HMA treatment, but worse survival.

Keywords: Primary myelodysplastic syndromes; TP53 mutation; mean corpuscular volume; prognosis.

MeSH terms

Chromosome Aberrations
Humans
Leukemia, Myeloid, Acute / genetics
Mutation
Myelodysplastic Syndromes* / diagnosis
Myelodysplastic Syndromes* / drug therapy
Myelodysplastic Syndromes* / genetics
Prognosis
Retrospective Studies
Treatment Outcome
Tumor Suppressor Protein p53* / genetics

Substances

TP53 protein, human
Tumor Suppressor Protein p53