TP53-mutated Myelodysplastic Syndromes Research Articles

TP53 Mutations in Acute Leukemias and Myelodysplastic Syndromes: Insights and Treatment Updates.

TP53 mutations are found in 5%-10% of de novo myelodysplastic syndrome (MDS) and AML cases. By contrast, in therapy related MDS and AML, mutations in TP53 are found in up to 30%-40% of patients. The majority of inactivating mutations observed in MDS and AML are missense mutations localized in a few prevalent hotspots. TP53 missense mutations together with truncating mutations or chromosomal loss of TP53 determine a loss-of-function effect on normal p53 function. Clonal expansion of TP53-mutant clones is observed under the selection pressure of chemotherapy or MDM2 inhibitor therapy. TP53-mutant clones are resistant to current chemotherapy, and when responses to treatment have been observed, they have correlated poorly with overall survival. The most heavily investigated and targeted agent for patients with TP53-mutant MDS and AML has been APR-246 (eprenetapopt) a p53 reactivator, in combination with azacitidine, but also in triplets with venetoclax. Despite positive results in phase II trials, a phase III trial did not confirm superior response or improved survival. Other agents, like magrolimab (anti-CD47 antibody), failed to demonstrate improved activity in TP53-mutant MDS and AML. Agents whose activity is not dependent on a functional apoptosis system like anti-CD123 antibodies or cellular therapies are in development and may hold promises. Delivering prognostic information in a dismal disease like TP53-mutated MDS and AML is particularly challenging. The physician should balance hope and realism, describing the trajectory of possible treatments and at the same time indicating the poor outcome, together with promoting adaptive coping in patients and elaborating on the nature of the disease.

TP53-Mutated Myelodysplastic Syndrome: A Diagnostic Approach in Different Clinical Settings.

TP53-Mutated Myelodysplastic Syndrome: A Diagnostic Approach in Different Clinical Settings.

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

ABSTRACTObjectiveTo explore the clinical outcomes and characteristics of TP53-mutated primary myelodysplastic syndromes (MDS).MethodsA 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.ResultsPatients were divided into two cohorts, the TP53-mutated type (TP53Mut) group (n = 19) and TP53 wild type (TP53WT) group (n = 55). Compared with the TP53WT group, patients in the TP53Mut 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 TP53Mut group had lower median MCV than the TP53WT 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 TP53Mut group (73.7% vs. 38.2%, P < 0.001). After 1–4 courses of HMA ± chemotherapy, the overall response rate of the TP53Mut group was higher than the TP53WT 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 TP53Mut group was significantly shorter than the TP53WT 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).ConclusionTP53-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.

Biological and clinical significance of TP53 mutations in myelodysplastic syndrome and acute myeloid leukemia

Anthracycline- and cytarabine-based intensive combination chemotherapies are considered the backbone therapy for patients with acute myeloid leukemia (AML). Although chemotherapy leads to long-term remission and cures many patients with AML, it can induce DNA damage/stress due to acute/chronic toxicities, acquired resistance, relapse, and therapy-related malignancies. Introduction of molecularly targeted agents with less systemic toxicities has considerably improved the scope of treatment, particularly in elderly and frail patients. However, outcomes of TP53-mutated myelodysplastic syndrome (MDS) and AML, a distinct group of myeloid disorders, have not improved irrespective of the treatment used (median overall survival, 5-10 months). In this review, we discuss the biological and clinical significance of TP53 mutations in malignancies, while particularly focusing on MDS/AML, and emerging therapies for TP53-mutated MDS/AML. Rationally designed novel treatment strategies are expected to improve the clinical outcomes of TP53-mutated MDS/AML.

Transplant for TP53-mutated MDS and AML: because we can or because we should?

TP53 mutations impair the cellular response to genotoxic stress and drive intrinsic resistance to conventional cytotoxic therapies. Clinical outcomes in patients with TP53-mutated myeloid malignancies are poor and marked by high-risk clinical features, such as complex karyotype and prior exposure to leukemogenic therapies, and short survival due to a high risk of relapse after allogeneic transplantation. TP53 mutations are thus included as adverse markers in clinical prognostic models, including European LeukemiaNet recommendations and the Molecular International Prognostic Scoring System for myelodysplastic syndromes (MDS). Recent data indicate that the TP53 allelic state, co-occurring somatic mutations, and the position of the TP53 mutation within the clonal hierarchy define genetic heterogeneity among TP53-mutated MDS and acute myeloid leukemia that may influence clinical outcomes, thereby informing the selection of patients most suitable for transplantation. Further, novel therapeutic methods such as antibody-based agents (monoclonals or dual-affinity retargeting antibodies), cellular therapies (natural killer cells, chimeric antigen receptor T cells), or targeted agents (eprenetapopt) may offer opportunities to modify the approach to pretransplant conditioning or posttransplant maintenance and improve clinical outcomes.

Smoking and Its Prognostic Effect on Survival in Patients with TP53 Mutated MDS

INTRODUCTION: Smoking is an established risk factor for myelodysplastic syndrome (MDS). While smoking has been shown to be correlated with TP53 mutation in multiple solid malignancies, and TP53 mutated MDS has been shown to have poorer survival, there is a paucity of data on the prognostic effect of smoking on survival in patients with TP53 mutated MDS. To further characterize this, we performed a retrospective study to investigate the relationship between smoking and survival in patients with TP53 mutated MDS. METHODS: After IRB approval, a total of 127 patients with MDS who were treated at Thomas Jefferson University Hospital from January 2016 to February 2020 were included in the study. All diagnoses were reviewed by a hematopathologist and TP53 mutation status was confirmed by in-house next generation sequencing. Patient data was collected from the date of MDS diagnosis until death or date of last follow up. Ever-smokers were defined as any patient with a history of tobacco smoking or current smokers, while non-smokers were defined as those with no history of tobacco smoking as documented in the electronic medical record. Data was also collected on revised international prognostic scoring system (R-IPSS) scores. Univariate associations were compared between variables of interest and smoking status. The Wilcoxon rank-sum test was used to assess difference between continuous variables and the chi-squared test was used to assess difference between categorical variables. RESULTS: Median overall survival (mOS) for the entire study cohort was 2.63 years (95% CI 2.10-4.29). In patients with TP53 mutations (n=35) we saw no survival difference between ever-smokers (0.64 years; 95% CI 0.30-1.19) and non-smokers (0.79 years; 95% CI 0.49-not reached), p=0.96. Overall, smokers had a shortened mOS (2.22 years; 95% CI 1.31-3.06) compared to never-smokers (4.30 years; 95% CI 2.62-7.61), trending towards significance with p=0.053. After stratification by smoking status, Caucasian smokers showed significantly reduced mOS (2.22 years; 95% CI 1.19-3.38) compared to non-smokers (5.65 years; 95% CI 3.23-7.8; p<0.05). Analysis looking at patients with high/very high risk R-IPSS scores also showed reduced survival for ever-smokers (0.64 years; 95% CI 0.53-0.88) compared to non-smokers (0.97 years; 95% CI 0.49-not reached), trending towards significance with p=0.06. For the whole cohort, high and very high risk IPSS-R scores (mOS 0.64; 95% CI 0.56-0.97) showed significantly reduced mOS compared to low and intermediate scores (mOS 4.49; 95% CI 2.8-7.74) with p<0.001. TP53 mutated MDS also showed decreased survival with mOS 0.64 years (95% CI 0.5-0.97) compared to mOS 4.49 years (95% CI 2.8-7.74) for wild type TP53 with p<0.001. CONCLUSION: We found no survival difference between ever-smokers and non-smokers in patient with TP53 mutated MDS. However, we did find a convincing trend towards poorer survival in ever-smokers compared to non-smokers in all patients, with a statistically significant reduction in survival in the Caucasian subgroup. Although there was no survival difference in the TP53 mutated cohort, the overall survival difference in the cohort as a whole suggests that smoking may play a role in more aggressive disease. Given the short survival time for TP53 mutated MDS, further studies with higher power may be required to distinguish survival differences. Future studies should also assess the impact of smoking on other cytogenetic and molecular subgroups of patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Characterization of TP53-Mutated Myelodysplastic Syndromes and Impact of Allelic Status and Concurrent Cytogenetic Abnormalities on Survival Outcomes

BackgroundTP53 mutations (TP53mt) are associated with dismal outcomes in myelodysplastic syndromes (MDS). However, clinical and biological heterogeneity among TP53mt MDS patients (pts) exists, including the prognostic relevance of mono- vs biallelic TP53mt. The newly proposed WHO 2022 and ICC 2022 classifications recognize TP53mt as a unique entity but vary in its definition. We aimed to assess the impact of TP53 allelic status and complex cytogenetics in different clinical subsets of TP53mt MDS. Methods A total of 2355 MDS pts with annotated clinical and molecular data treated at Moffitt Cancer Center were analyzed. We defined MDS with biallelic TP53 inactivation (biTP53) according to the 5th edition of the WHO classification. Biallelic status was determined by VAF ≥50%, 2 or more TP53mt and/or TP53mt with deletion 17/17p abnormalities. Pts were classified into IPSS-R lower risk (LR) and higher risk (HR) strata by merging IPSS-R VL, L and I categories, as well as H and VH groups. Results A total of 490 pts (21%) harbored a TP53mt. Of these, 78% (382) were biTP53 and 22% (108) maTP53. Median duration of follow-up was 4.7 years (4.4-4.9). Pts harboring TP53mt had significantly shorter OS relative to their TP53wt counterparts: median OS 1.2 yrs vs 4 yrs (p<.001). Median OS was worse for the biTP53 subset compared to maTP53: 1.0 yrs (0.9-1.1) vs 1.3 yrs (1.1-1.6; p<.001). Compared to those harboring TP53wt, pts with maTP53 had double the risk of death: HR 2.1 (1.8-2.5). For pts with biTP53 the risk quadrupled: HR 4.0 (3.4-4.7). Both were significant at p<.001. Patients harboring complex (CK) vs non-complex (nCK) karyotypes had inferior mOS of 1.0 yrs (0.9-1.1) vs 2.1 yrs (1.5-2.7; p<.001). Compared to TP53wt, the risk of death was higher for TP53 with CK [HR 4.7 (4.1-5.4)] than for TP53 with nCK [HR 1.5 (1.2-1.8)], both significant at p<.001. Among patients with nCK, allelic state had significant impact on outcomes: mOS for maTP53 was 2.8 yrs (2.0-3.6) vs 1.2 yrs (0.6-1.8) for biTP53 (p<.001; Figure 1). Compared to TP53wt, HR for death for maTP53 was 1.2 (0.9-1.5, p=.21) and for biTP53 was 2.7 (1.9-3.8, p<.001). There was no survival distinction between maTP53 and biTP53 among pts with CK (p=0.780; Figure 1). Both had mOS of 1 yr (0.9-1.2) and were associated with worse outcomes compared to CK TP53wt (p<0.001). Among pts with LR disease, outcomes were significantly worse for those harboring TP53mt: mOS for TP53wt was 5.2 yrs (4.7-5.7) compared to 3.3 yrs (1.6-5.0, p<.001) for maTP53 and 2.1 yrs (0-4.4, p<.001) for biTP53. There were no differences between maTP53 and biTP53 (p=.2). Allelic status remained significant in HR disease (p=.033), where mOS was worse for biTP53 compared to maTP53: 0.9 yrs (0.8-1.0) vs 1.1 yrs (1.0-1.2). Similarly, allelic state had value in pts with <5% and ≥5% blasts. Among pts with <5% blasts, TP53wt mOS was 4.8 yrs (4.3-5.4) vs 2.5 yrs (1.7-3.3) for maTP53 and 1.3 yrs (0.9-1.7) for biTP53 (p=.032). Outcomes were worse among TP53mt pts with ≥5% blasts: mOS for TP53wt was 1.7 yrs (1.6-1.9), with distinction between maTP53 and biTP53: 1.2 yrs (1.0-1.2) and 0.9 yrs (0.8-1.0) respectively (p=.005). For the <5% group, the median VAF in maTP53 was 19.5% and 40% in biTP53. For the ≥5% group, the median VAF in maTP53 was 24% (95) and 47.3% (158) in biTP53. There were no differences in outcomes using 10% blast burden as cutoff. ConclusionTP53mt MDS demarcates a heterogenous group, whose behavior is influenced by allelic status and cytogenetic architecture. TP53mt patients have poor prognosis with ≥5% blasts without distinction from a 10% cutoff. In TP53mt disease, allelic state has strong significance in pts with non-CK, and retains significance independent of IPSS-R strata and myeloblast percentage, albeit with marginal differences. Notably, CK matters independent of allelic status and is invariably associated with worse outcomes. TP53mt with CK should homogenously be considered a biallelic equivalent. This has important implications for future trial design where distinction of allelic state and CK carries relevance. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

150 - Outcomes with Allogeneic Hematopoietic Stem Cell Transplantation in TP53-Mutated Myelodysplastic Syndromes: A Systematic Review and Meta-Analysis

150 - Outcomes with Allogeneic Hematopoietic Stem Cell Transplantation in TP53-Mutated Myelodysplastic Syndromes: A Systematic Review and Meta-Analysis

What Are the Prospects for Treating TP53 Mutated Myelodysplastic Syndromes and Acute Myeloid Leukemia?

TP53 is a key tumor suppressor gene involved in fundamental biological processes of genomic stability and is recurrently mutated in a subgroup of myelodysplastic syndromes and acute myeloid leukemia. These patients have unique clinical and molecular features resulting in dismal outcomes despite standard cytotoxic chemotherapy, and long-term survival is seldom achieved with allogeneic stem cell transplant. Upfront use of hypomethylating agents with or without venetoclax has resulted in a favorable initial response over intensive cytotoxic chemotherapy, albeit responses are nondurable, and the median overall survival is typically less than 6 to 8 months. In this review, we examine the evidence of conventional treatments and focus on the emerging novel therapeutic options, including targeted molecular and immunotherapies for this challenging molecular subgroup. Together, there are still significant unmet needs to improve outcomes of patients with TP53 mutated myelodysplastic syndromes and acute myeloid leukemia, and enrollment in clinical trials should be highly favored whenever they are available.

TP53 Combined Phenotype Score Is Associated with the Clinical Outcome of TP53-Mutated Myelodysplastic Syndromes.

Simple SummaryTP53 is the most frequently mutated genes in cancer, and mutations of TP53 are observed in 5–10% of patients in myelodysplastic syndrome (MDS). In patients with MDS, TP53 mutations are associated with adverse outcomes; however, there is still significant heterogeneity in these disease courses. We performed retrospective review of 107 patients with untreated TP53-mutated MDS, and identified that the functional impact of TP53 mutations, represented by phenotypic annotation of TP53 mutations (PHANTM) combined phenotype score is associated with prognosis. In patients with TP53-mutated MDS, we found that a higher PHANTM combined phenotype score is associated with poorer clinical outcome, and this has independent influence on prognosis accounting for IPSS-R and other risk variables. Our findings suggest that TP53-mutated MDS is heterogeneous and not all TP53 mutations harbor the same impact on prognosis. The PHANTM combined score adds to prognostic precision in MDS beyond previously reported TP53 allelic state.Mutations of TP53 are observed in 5–10% of patients in myelodysplastic syndrome (MDS) and are associated with adverse outcomes. Previous studies indicate that the TP53 allelic state and variant allele frequency of TP53 mutation impact patient outcomes, but there is significant heterogeneity within this MDS subgroup. We performed retrospective review of clinicopathologic and genomic information of 107 patients with TP53-mutated MDS. We assessed each mutation according to the phenotypic annotation of TP53 mutations (PHANTM) and analyzed the associations between predicted TP53 mutant function, represented by the PHANTM combined phenotype score, and overall survival (OS) using the log rank test and Cox regression. Our results indicated that patients with PHANTM combined phenotype score above the median (>1) had significantly shorter OS compared to those with scores below the median (median OS: 10.59 and 16.51 months, respectively, p = 0.025). This relationship remained significant in multivariable analysis (HR (95%CI): 1.62 (1.01–2.58), p = 0.044) and identified to have an independent prognostic influence, accounting for known risk such as IPSS-R and other standard risk variables. Our results suggest that the functional information of TP53 mutations, represented by PHANTM combined phenotype score, are associated with the clinical outcome of patients with TP53-mutated MDS.

Personalized Medicine for TP53 Mutated Myelodysplastic Syndromes and Acute Myeloid Leukemia.

Targeting TP53 mutated myelodysplastic syndromes and acute myeloid leukemia remains a significant unmet need. Recently, new drugs have attempted to improve the outcomes of this poor molecular subgroup. The aim of this article is to review all the current knowledge using active agents including hypomethylating agents with venetoclax, eprenetapopt or magrolimab. We include comprehensive analysis of clinical trials to date evaluating these drugs in TP53 myeloid neoplasms as well as discuss future novel combinations for consideration. Additionally, further understanding of the unique clinicopathologic components of TP53 mutant myeloid neoplasms versus wild-type is critical to guide future study. Importantly, the clinical trajectory of patients is uniquely tied with the clonal burden of TP53, which enables serial TP53 variant allele frequency analysis to be a critical early biomarker in investigational studies. Together, significant optimism is now possible for improving outcomes in this patient population.

Drugging the Master Regulator TP53 in Cancer: Mission Possible?

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES Eprenetapopt Plus Azacitidine in TP53-Mutated Myelodysplastic Syndromes and Acute Myeloid Leukemia: A Phase II Study by the Groupe Francophone des Myélodysplasies (GFM). February 18, 2021 ARTICLE CITATION DOI: 10.1200/JCO.21.00192 Journal of Clinical Oncology - published online before print April 2, 2021 PMID: 33797953 Drugging the Master Regulator TP53 in Cancer: Mission Possible? Giovanni Blandino , MD1xGiovanni BlandinoSearch for articles by this author Show More 1Oncogenomic and Epigenetic Unit, Department of Research, Advanced Diagnostic and Technological Innovation, Regina Elena National Cancer Institute, Rome, Italy https://doi.org/10.1200/JCO.21.00192 First Page Full Text PDF Figures and Tables © 2021 by American Society of Clinical OncologySUPPORTSupported by the Italian Association for Cancer Research (AIRC).AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTDrugging the Master Regulator TP53 in Cancer: Mission Possible?The following represents disclosure information provided by the author of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).No potential conflicts of interest were reported. Companion Eprenetapopt Plus Azacitidine in TP53-Mutated Myelodysplastic Syndromes and Acute Myeloid Leukemia: A Phase II Study by the Groupe Francophone des Myélodysplasies (GFM)

Evolutionary Action Score Identifies a Subset of TP53 Mutated Myelodysplastic Syndrome with Favorable Prognosis

Evolutionary Action Score Identifies a Subset of TP53 Mutated Myelodysplastic Syndrome with Favorable Prognosis

TP53 in Myelodysplastic Syndromes: Recent Biological and Clinical Findings.

TP53 dysregulation plays a pivotal role in the molecular pathogenesis of myelodysplastic syndromes (MDS), identifying a subgroup of patients with peculiar features. In this review we report the recent biological and clinical findings of TP53-mutated MDS, focusing on the molecular pathways activation and on its impact on the cellular physiology. In MDS, TP53 mutational status is deeply associated with del(5q) syndrome and its dysregulation impacts on cell cycle, DNA repair and apoptosis inducing chromosomal instability and the clonal evolution of disease. TP53 defects influence adversely the MDS clinical outcome and the treatment response rate, thus new therapeutic approaches are being developed for these patients. TP53 allelic state characterization and the mutational burden evaluation can therefore predict prognosis and identify the subgroup of patients eligible for targeted therapy. For these reasons, in the era of precision medicine, the MDS diagnostic workup cannot do without the complete assessment of TP53 mutational profile.

Genomic context and TP53 allele frequency define clinical outcomes in TP53-mutated myelodysplastic syndromes

AbstractTP53 mutations are associated with adverse outcomes and shorter response to hypomethylating agents (HMAs) in myelodysplastic syndrome (MDS). Limited data have evaluated the impact of the type, number, and patterns of TP53 mutations in response outcomes and prognosis of MDS. We evaluated the clinicopathologic characteristics, outcomes, and response to therapy of 261 patients with MDS and TP53 mutations. Median age was 68 years (range, 18-80 years). A total of 217 patients (83%) had a complex karyotype. TP53 mutations were detected at a median variant allele frequency (VAF) of 0.39 (range, 0.01-0.94). TP53 deletion was associated with lower overall response rate (ORR) (odds ratio, 0.3; P = .021), and lower TP53 VAF correlated with higher ORR to HMAs. Increase in TP53 VAF at the time of transformation was observed in 13 patients (61%), and previously undetectable mutations were observed in 15 patients (65%). TP53 VAF was associated with worse prognosis (hazard ratio, 1.02 per 1% VAF increase; 95% confidence interval, 1.01-1.03; P < .001). Integration of TP53 VAF and karyotypic complexity identified prognostic subgroups within TP53-mutant MDS. We developed a multivariable model for overall survival that included the revised International Prognostic Scoring System (IPSS-R) categories and TP53 VAF. Total score for each patient was calculated as follows: VAF TP53 + 13 × IPSS-R blast score + 16 × IPSS-R cytogenetic score + 28 × IPSS-R hemoglobin score + 46 × IPSS-R platelet score. Use of this model identified 4 prognostic subgroups with median survival times of not reached, 42.2, 21.9, and 9.2 months. These data suggest that outcomes of patients with TP53-mutated MDS are heterogeneous and that transformation may be driven not only by TP53 but also by other factors.

2019 Brings Biologic Understanding and Hope for Patients With TP53 Mutated Myelodysplastic Syndrome

2019 Brings Biologic Understanding and Hope for Patients With TP53 Mutated Myelodysplastic Syndrome

Evolutionary Action (EA) Score of TP53 Mutations Defines Prognostic Subsets within TP53 Mutated Myelodysplastic Syndromes and Acute Myeloid Leukemia

Evolutionary Action (EA) Score of TP53 Mutations Defines Prognostic Subsets within TP53 Mutated Myelodysplastic Syndromes and Acute Myeloid Leukemia

Genomic Context and TP53 Allele Frequency Define Prognostic Subgroups and Response Outcomes in TP53 Mutated Myelodysplastic Syndromes

Genomic Context and TP53 Allele Frequency Define Prognostic Subgroups and Response Outcomes in TP53 Mutated Myelodysplastic Syndromes

APR-246 Combined with Azacitidine (AZA) in TP53 Mutated Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML). a Phase 2 Study By the Groupe Francophone Des Myélodysplasies (GFM)

APR-246 Combined with Azacitidine (AZA) in TP53 Mutated Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML). a Phase 2 Study By the Groupe Francophone Des Myélodysplasies (GFM)

TP53 State Dictates Genome Stability, Clinical Presentation and Outcomes in Myelodysplastic Syndromes

TP53 State Dictates Genome Stability, Clinical Presentation and Outcomes in Myelodysplastic Syndromes