Relationship between p53 expression and prognosis of myelodysplastic syndrome treated with azacitidine
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ORIGINAL ARTICLE
Relationship between p53 expression and prognosis of myelodysplastic syndrome treated with azacitidine Satoko Oka 1 & Kazuo Ono 2 & Masaharu Nohgawa 1 Received: 30 June 2020 / Accepted: 13 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract We previously demonstrated that a CD13/CD33 ratio low (< 1) and high (≥ 2) was associated with shorter survival in patients with myelodysplastic syndromes (MDS) treated with azacitidine (AZA). Previous studies also showed the negative impact of TP53 mutations on patient outcomes. The aim of the study is to investigate the relationship between a p53 expression, CD13/CD33 ratio, and the outcomes of MDS patients treated with AZA. The relationship between the p53 expression, CD13/CD33 ratio in blast cells, and outcomes of 121 MDS patients treated with AZA was examined. In patients with CD13/CD33 ratio low and high, there was no significant difference in survival between p53-positive and p53-negative patients. However, in the patients with 1 ≤ CD13/CD33 ratio < 2, p53 positivity correlated with higher serum LDH levels. Poorer risk status according to cytogenetics was more frequently observed in p53-positive patients than in p53-negative patients. The rates of progressive disease and failure after 4 cycles of AZA were higher in p53-positive patients than in p53-negative patients. Univariate and multivariate analyses confirmed that higher serum LDH levels and p53 positivity were independent adverse prognostic factors for prognosis. A Kaplan-Meier analysis revealed the potential of p53 expression as a prognostic factor in patients with 1 ≤ CD13/CD33 ratio < 2 and that it correlated with shorter survival and acute myeloid leukemia (AML) progression. The present study showed that p53 expression is an independent risk factor for shorter overall survival and AML progression in MDS patients with 1 ≤ CD13/CD33 ratio < 2. Keywords Myelodysplastic syndromes . Azacitidine . CD13 . CD33 . p53
Introduction The hypomethylating agent, azacitidine (AZA), is an effective therapy for low- and high-risk myelodysplastic syndromes (MDS) [1]. MDS are a group of clonal hematological disorders that are characterized by ineffective hematopoiesis, leading to blood cytopenias and a high risk of progression to acute myeloid leukemia (AML) [2]. Approximately 50% of patients respond to AZA, and, thus, prognostic factors for responses and
* Satoko Oka [email protected] 1
Division of Hematology, Japanese Red Cross Society Wakayama Medical Center, Wakayama, Japan
2
Division of Pathology, Japanese Red Cross Society Wakayama Medical Center, Wakayama, Japan
survival need to be clarified in MDS patients treated with AZA. We recently reported that the CD13/CD33 ratio in blast cells from MDS patients treated with AZA was associated with patient outcomes independent of other prognostic factors and the estimated 5-year overall survival (OS) rate was significantly lower in CD13/ CD33 low (< 1) or high (≥ 2) than in 1 ≤ CD13/CD33 ratio < 2 (22% vs. 58%, p = 0.015) [3]
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