Multilineage Dysplasia as Assessed by Immunophenotype in Acute Myeloid Leukemia: A Prognostic Tool in a Genetically Undefined Category

Acute myeloid leukemia (AML) “with myelodysplasia-related changes (MRC)” is considered a separate entity by the World Health Organization (WHO) classification of myeloid neoplasms. While anamnestic and cytogenetic criteria provide objective attribution to this subset, with clear unfavorable prognostic significance, the actual role of multi-lineage dysplasia (MLD) as assessed by morphology is debated. The aim of our work was to study MLD by a technique alternative to morphology, which is multiparameter flow cytometry (MFC), in a large series of 302 AML patients intensively treated at our Center. The correlation with morphology we observed in the unselected analysis reiterated the capability of the MFC-based approach at highlighting dysplasia. MLD data, estimated through an immune-phenotypic score (IPS), provided no insight into prognosis when considered overall nor within well-defined genetic categories. Of interest, IPS-related dysplasia conveyed significant prognostic information when we focused on genetically undefined patients, triple-negative for NPM1, FLT3 and CEBPA (TN-AML). In this context, the lack of dysplastic features (IPS_0) correlated with a significantly higher CR rate and longer survival compared to patients showing dysplasia in one or both (neutrophil and erythroid) cell lineages. The impact of IPS category maintained its validity after censoring at allogeneic HSCT and in a multivariate analysis including baseline and treatment-related covariates. In a subgroup featured by the lack of genetic determinants, our data could help address the relative unmet needs in terms of risk assessment and treatment strategy, and provide insight into prediction of response in the rapidly evolving therapeutic scenario of AML.

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Low expression of MN1 associates with better treatment response in older patients with de novo cytogenetically normal acute myeloid leukemia

Blood ◽

10.1182/blood-2011-06-357764 ◽

2011 ◽

Vol 118 (15) ◽

pp. 4188-4198 ◽

Cited By ~ 40

Author(s):

Sebastian Schwind ◽

Guido Marcucci ◽

Jessica Kohlschmidt ◽

Michael D. Radmacher ◽

Krzysztof Mrózek ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Older Patients ◽

Myeloid Leukemia ◽

Hox Genes ◽

De Novo ◽

Prognostic Significance ◽

The Impact ◽

Favorable Group ◽

Acute Myeloid

AbstractLow MN1 expression bestows favorable prognosis in younger adults with cytogenetically normal acute myeloid leukemia (CN-AML), but its prognostic significance in older patients is unknown. We analyzed pretherapy MN1 expression in 140 older (≥ 60 years) de novo CN-AML patients treated on cytarabine/daunorubicin-based protocols. Low MN1 expressers had higher complete remission (CR) rates (P = .001), and longer overall survival (P = .03) and event-free survival (EFS; P = .004). In multivariable models, low MN1 expression was associated with better CR rates and EFS. The impact of MN1 expression on overall survival and EFS was predominantly in patients 70 years of age or older, with low MN1 expressers with mutated NPM1 having the best outcome. The impact of MN1 expression was also observed in the Intermediate-I, but not the Favorable group of the European LeukemiaNet classification, where low MN1 expressers had CR rates and EFS similar to those of Favorable group patients. MN1 expresser-status-associated gene- and microRNA-expression signatures revealed underexpression of drug resistance and adverse outcome predictors, and overexpression of HOX genes and HOX-gene–embedded microRNAs in low MN1 expressers. We conclude that low MN1 expression confers better prognosis in older CN-AML patients and may refine the European LeukemiaNet classification. Biologic features associated with MN1 expression may help identify new treatment targets.

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Measurable Residual Disease Detected by Multiparameter Flow Cytometry and Sequencing Improves Prediction of Relapse and Survival in Acute Myeloid Leukemia

Frontiers in Oncology ◽

10.3389/fonc.2021.677833 ◽

2021 ◽

Vol 11 ◽

Author(s):

Fu-Jia Liu ◽

Wen-Yan Cheng ◽

Xiao-Jing Lin ◽

Shi-Yang Wang ◽

Tian-Yi Jiang ◽

...

Keyword(s):

Flow Cytometry ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Residual Disease ◽

Prognostic Significance ◽

Multiparameter Flow Cytometry ◽

Net Reclassification Improvement ◽

Measurable Residual Disease ◽

Acute Myeloid ◽

Time Point

The clinically ideal time point and optimal approach for the assessment of measurable residual disease (MRD) in patients with acute myeloid leukemia (AML) are still inconclusive. We investigated the clinical value of multiparameter flow cytometry-based MRD (MFC MRD) after induction (n = 492) and two cycles of consolidation (n = 421). The latter time point was proved as a superior indicator with independent prognostic significance for both relapse-free survival (RFS, HR = 3.635, 95% CI: 2.433–5.431, P <0.001) and overall survival (OS: HR = 3.511, 95% CI: 2.191–5.626, P <0.001). Furthermore, several representative molecular MRD markers were compared with the MFC MRD. Both approaches can establish prognostic value in patients with NPM1 mutations, and FLT3, C-KIT, or N-RAS mutations involved in kinase-related signaling pathways, while the combination of both techniques further refined the risk stratification. The detection of RUNX1–RUNX1T1 fusion transcripts achieved a considerable net reclassification improvement in predicting the prognosis. Conversely, for patients with biallelic CEBPA or DNMT3A mutations, only the MFC method was recommended due to the poor prognostic discriminability in tracking mutant transcripts. In conclusion, this study demonstrated that the MFC MRD after two consolidation cycles independently predicted clinical outcomes, and the integration of MFC and molecular MRD should depend on different types of AML-related genetic lesions.

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Defining minimal residual disease in acute myeloid leukemia: which platforms are ready for “prime time”?

Blood ◽

10.1182/blood-2014-05-577593 ◽

2014 ◽

Vol 124 (23) ◽

pp. 3345-3355 ◽

Cited By ~ 149

Author(s):

David Grimwade ◽

Sylvie D. Freeman

Keyword(s):

Acute Myeloid Leukemia ◽

Minimal Residual Disease ◽

Myeloid Leukemia ◽

Residual Disease ◽

Multiparameter Flow Cytometry ◽

Molecular Heterogeneity ◽

Prognostic Information ◽

Reliable Determination ◽

Minimal Residual ◽

Acute Myeloid

Abstract The past 40 years have witnessed major advances in defining the cytogenetic aberrations, mutational landscape, epigenetic profiles, and expression changes underlying hematological malignancies. Although it has become apparent that acute myeloid leukemia (AML) is highly heterogeneous at the molecular level, the standard framework for risk stratification guiding transplant practice in this disease remains largely based on pretreatment assessment of cytogenetics and a limited panel of molecular genetic markers, coupled with morphological assessment of bone marrow (BM) blast percentage after induction. However, application of more objective methodology such as multiparameter flow cytometry (MFC) has highlighted the limitations of morphology for reliable determination of remission status. Moreover, there is a growing body of evidence that detection of subclinical levels of leukemia (ie, minimal residual disease, MRD) using MFC or molecular-based approaches provides powerful independent prognostic information. Consequently, there is increasing interest in the use of MRD detection to provide early end points in clinical trials and to inform patient management. However, implementation of MRD assessment into clinical practice remains a major challenge, hampered by differences in the assays and preferred analytical methods employed between routine laboratories. Although this should be addressed through adoption of standardized assays with external quality control, it is clear that the molecular heterogeneity of AML coupled with increasing understanding of its clonal architecture dictates that a “one size fits all” approach to MRD detection in this disease is not feasible. However, with the range of platforms now available, there is considerable scope to realistically track treatment response in every patient.

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Prognostic Significance of Expression of a Single MicroRNA,miR-181a, in Cytogenetically Normal Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study

Journal of Clinical Oncology ◽

10.1200/jco.2010.29.2953 ◽

2010 ◽

Vol 28 (36) ◽

pp. 5257-5264 ◽

Cited By ~ 137

Author(s):

Sebastian Schwind ◽

Kati Maharry ◽

Michael D. Radmacher ◽

Krzysztof Mrózek ◽

Kelsi B. Holland ◽

...

Keyword(s):

Gene Expression ◽

Acute Myeloid Leukemia ◽

Gene Expression Profile ◽

Expression Profile ◽

Myeloid Leukemia ◽

Prognostic Significance ◽

Comprehensive Cancer Center ◽

Wild Type ◽

The Impact ◽

Acute Myeloid

PurposeTo evaluate the prognostic significance of expression levels of a single microRNA, miR-181a, in the context of established molecular markers in cytogenetically normal acute myeloid leukemia (CN-AML), and to gain insight into the leukemogenic role of miR-181a.Patients and MethodsmiR-181a expression was measured in pretreatment marrow using Ohio State University Comprehensive Cancer Center version 3.0 arrays in 187 younger (< 60 years) adults with CN-AML. Presence of other molecular prognosticators was assessed centrally. A gene-expression profile associated with miR-181a expression was derived using microarrays and evaluated by Gene-Ontology analysis.ResultsHigher miR-181a expression associated with a higher complete remission (CR) rate (P = .04), longer overall survival (OS; P = .01) and a trend for longer disease-free survival (DFS; P = .09). The impact of miR-181a was most striking in poor molecular risk patients with FLT3-internal tandem duplication (FLT3-ITD) and/or NPM1 wild-type, where higher miR-181a expression associated with a higher CR rate (P = .009), and longer DFS (P < .001) and OS (P < .001). In multivariable analyses, higher miR-181a expression was significantly associated with better outcome, both in the whole patient cohort and in patients with FLT3-ITD and/or NPM1 wild-type. These results were also validated in an independent set of older (≥ 60 years) patients with CN-AML. A miR-181a-associated gene-expression profile was characterized by enrichment of genes usually involved in innate immunity.ConclusionTo our knowledge, we provide the first evidence that the expression of a single microRNA, miR-181a, is associated with clinical outcome of patients with CN-AML and may refine their molecular risk classification. Targeted treatments that increase endogenous levels of miR-181a might represent novel therapeutic strategies.

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Clonal Heterogeneity As Detected by Metaphase Karyotyping Is an Indicator of Poor Prognosis in Acute Myeloid Leukemia

Journal of Clinical Oncology ◽

10.1200/jco.2013.50.7921 ◽

2013 ◽

Vol 31 (31) ◽

pp. 3898-3905 ◽

Cited By ~ 44

Author(s):

Tilmann Bochtler ◽

Friedrich Stölzel ◽

Christoph E. Heilig ◽

Christina Kunz ◽

Brigitte Mohr ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Poor Prognosis ◽

Clonal Evolution ◽

Prognostic Significance ◽

Genomic Diversity ◽

Prognostic Information ◽

Clonal Heterogeneity ◽

Landmark Analyses ◽

Acute Myeloid

Purpose In acute myeloid leukemia (AML), studies based on whole-genome sequencing have shown genomic diversity within leukemic clones. The aim of this study was to address clonal heterogeneity in AML based on metaphase cytogenetics. Patients and Methods This analysis included all patients enrolled onto two consecutive, prospective, randomized multicenter trials of the Study Alliance Leukemia. Patients were newly diagnosed with non-M3 AML and were fit for intensive chemotherapy. Results Cytogenetic subclones were detected in 418 (15.8%) of 2,639 patients from the whole study population and in 418 (32.8%) of 1,274 patients with aberrant karyotypes. Among those, 252 karyotypes (60.3%) displayed a defined number of distinct subclones, and 166 (39.7%) were classified as composite karyotypes. Subclone formation was particularly frequent in the cytogenetically adverse group, with subclone formation in 69.0%, 67.1%, and 64.8% of patients with complex aberrant, monosomal, and abnl(17p) karyotypes (P < .001 each). Two-subclone patterns typically followed a mother-daughter evolution, whereas for ≥ three subclones, a branched pattern prevailed. In non–core binding factor AML, subclone formation was associated with inferior event-free and overall survival and was confirmed as an independent predictor of poor prognosis in multivariate analysis. Subgroup analysis showed that subclone formation adds prognostic information particularly in the cytogenetic adverse-risk group. Allogeneic stem-cell transplantation improved the prognosis of patients with subclone karyotypes as shown in landmark analyses. Conclusion Cytogenetic subclones are frequent in AML and permit tracing of clonal evolution and architecture. They bear prognostic significance with clonal heterogeneity as an independent adverse prognostic marker in cytogenetically adverse-risk AML.

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Defining minimal residual disease in acute myeloid leukemia: which platforms are ready for “prime time”?

Hematology ◽

10.1182/asheducation.v2014.1.222.3884425 ◽

2014 ◽

Vol 2014 (1) ◽

pp. 222-233 ◽

Cited By ~ 3

Author(s):

David Grimwade ◽

Sylvie D. Freeman

Keyword(s):

Acute Myeloid Leukemia ◽

Minimal Residual Disease ◽

Myeloid Leukemia ◽

Residual Disease ◽

Multiparameter Flow Cytometry ◽

Molecular Heterogeneity ◽

Prognostic Information ◽

Reliable Determination ◽

Minimal Residual ◽

Acute Myeloid

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Prognostic Significance of CD56 Antigen Expression in Patients with De Novo Non-M3 Acute Myeloid Leukemia

BioMed Research International ◽

10.1155/2021/1929357 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Yanni Sun ◽

Jia Wan ◽

Qiuyue Song ◽

Chengxin Luo ◽

Xi Li ◽

...

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

De Novo ◽

Prognostic Significance ◽

Cutoff Point ◽

Multiparameter Flow Cytometry ◽

Poor Overall Survival ◽

Cd56 Expression ◽

Acute Myeloid

Acute myeloid leukemia (AML) is a heterogeneous group of disorders with distinct characteristics and prognoses. Although cytogenetic changes and gene mutations are associated with AML prognosis, there is a need to identify further factors. CD56 is considered a prognostic factor for AML, which is abnormally expressed in leukemia cells. However, a clear consensus for this surface molecule is lacking, which has prompted us to investigate its prognostic significance. Bone marrow samples of de novo non-M3 AML were collected to detect CD56 expression using multiparameter flow cytometry (FCM). As a result, the CD56 expression in de novo non-M3 AML was found to be significantly higher than that in acute lymphoma leukemia (ALL, P = 0.017 ) and healthy controls ( P = 0.02 ). The X-Tile program produced a CD56 cutoff point at a relative expression level of 24.62%. Based on this cutoff point, high CD56 expression was observed in 29.21% of de novo non-M3 AML patients. CD56-high patients had a poor overall survival (OS, P = 0.015 ) compared to CD56-low patients. Bone marrow transplantation (BMT) improved OS ( P = 0.004 ), but a poor genetic risk was associated with an inferior OS ( P = 0.002 ). Compared with CD56-low patients, CD56-high patients had lower peripheral blood platelet (PLT) counts ( P = 0.010 ). Our research confirmed that high CD56 expression is associated with adverse clinical outcomes in de novo non-M3 AML patients, indicating that CD56 could be used as a prognostic marker for a more precise stratification of de novo non-M3 AML patients.

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Determination of relapse risk based on assessment of minimal residual disease during complete remission by multiparameter flow cytometry in unselected patients with acute myeloid leukemia

Blood ◽

10.1182/blood-2004-03-1036 ◽

2004 ◽

Vol 104 (10) ◽

pp. 3078-3085 ◽

Cited By ~ 176

Author(s):

Wolfgang Kern ◽

Daniela Voskova ◽

Claudia Schoch ◽

Wolfgang Hiddemann ◽

Susanne Schnittger ◽

...

Keyword(s):

Flow Cytometry ◽

Acute Myeloid Leukemia ◽

Complete Remission ◽

Myeloid Leukemia ◽

Residual Disease ◽

Multiparameter Flow Cytometry ◽

Consolidation Therapy ◽

Prognostic Information ◽

Minimal Residual ◽

Acute Myeloid

Abstract Quantification of minimal residual disease (MRD) reveals significant prognostic information in patients treated for acute myeloid leukemia (AML). The application of multiparameter flow cytometry (MFC) for MRD assessment has resulted in significant prognostic information in selected cases in previous analyses. We analyzed MRD in unselected patients with AML in complete remission (CR) after induction (n = 58) and consolidation (n = 62) therapies. By using a comprehensive panel of monoclonal antibodies we identified at least one leukemia-associated aberrant immunophenotype (LAIP) in each patient. The degree of reduction between diagnosis and CR in LAIP-positive cells (log difference [LD]) as a continuous variable was significantly related to relapse-free survival (RFS) both after induction (P = .0001) and consolidation (P = .000 08) therapies, respectively. The LD determined after consolidation therapy was the only parameter related to overall survival (OS) (P = .005). Separation of patients based on the 75th percentile of LD after consolidation therapy resulted in groups with highly different RFS (83.3% versus 25.7%, P = .0034) and OS (87.5% versus 51.4%, P = .0507) at 2 years. Multivariate analysis identified LD as an independent prognostic factor for RFS at both checkpoints. MFC-based quantification of MRD reveals important prognostic information in unselected patients with AML in addition to cytogenetics and should be further evaluated and used in clinical trials.

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NUP98/NSD1 Translocation Further Risk-Stratifies Patients With FLT3/ITD In Acute Myeloid Leukemia: A Report From Children’s Oncology Group and SWOG

Blood ◽

10.1182/blood.v122.21.488.488 ◽

2013 ◽

Vol 122 (21) ◽

pp. 488-488

Author(s):

Fabiana Ostronoff ◽

Megan Othus ◽

Robert B. Gerbing ◽

Michael R. Loken ◽

Susana C Raimondi ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Clinical Outcome ◽

Myeloid Leukemia ◽

Prognostic Significance ◽

Building Blocks ◽

Nuclear Pore ◽

Disease Characteristics ◽

The Impact ◽

Very High ◽

Acute Myeloid

Abstract Nucleoporins (NUP) are a family of proteins that form the building blocks of the nuclear pore complex. Translocations involving NUP family members have been reported in acute myeloid leukemia (AML) as predictors of poor outcome. Using whole transcript sequencing we identified NUP98/NSD1 translocations in 2 AML patients; both were cytogenetically normal (CN) and harbored FLT3/ITD. We therefore performed a comprehensive study on the prevalence of NUP98/NSD1 in children and adult AML patients to define the prognostic significance of this translocation and its contribution to clinical outcome. NUP98/NSD1 was evaluated using RT-PCR and the fusion transcripts were verified by Sanger sequencing. Presence of NUP98/NSD1 transcript was initially assessed on all available diagnostic specimens from patients treated in COG AAML03P1. As this transcript was detected only in patients with CN-AML or FLT3/ITD, the remaining evaluations on CCG2961, COG AAML0531 and SWOG0106 were limited to this patient population. Presence of NUP98/NSD1 was correlated with disease characteristics and clinical outcome. We initially assessed the impact of the NUP98/NSD1 in children with FLT3/ITD. Of the 2486 patients treated in 3 pediatric trials (age >1 month to < 30 years), 373 had FLT3/ITD (15%), of whom 16% also harbored NUP98-NSD1. Demographics and disease characteristics of FLT3/ITD patients were compared between those with and without NUP98/NSD1. NUP98/NSD1 was significantly associated with younger age, intermediate risk cytogenetics, higher marrow blast %, white blood and platelet count. Mutations in NPM1 and CEBPA were not detected in those with dual FLT3/ITD and NUP98/NSD1 alterations, whereas WT1 was enriched in these patients as compared to those with FLT3/ITD without NUP98/NSD1 (40.6% vs 17.3%, p=0.004). Patients with FLT3/ITD who also harbored NUP98/NSD1 had significantly worse complete remission (CR) rates (28% vs 69%, p<0.001), overall survival (3-year OS 32% vs 55%, p=0.004) and event-free survival (3-year EFS 16% vs 38%, p<0.001) than those with FLT3/ITD without NUP98/NSD1. Minimal residual disease (MRD) was also significantly higher in patients with dual FLT3/ITD and NUP98/NSD1 alterations as compared to those with FLT3/ITD without NUP98/NSD1 (76% vs 36.5%, p<0.0029). Within the FLT3/ITD cohort, in multivariate analysis including other known prognostic factors (such as cytogenetics, WBC, bone marrow blast %, NPM1, CEBPA and WT1), NUP98/NSD1 remained an independent predictor of poor CR rate. In CN-AML pediatric patients (N=267), the prevalence NUP98/NSD1 was 8%, of which 73% of were also FLT3/ITD. The CR rate for CN-AML harboring NUP98/NSD1 was significantly lower than in those without it (50% vs. 78%, p=0.008) and patients with both NUP98/NSD1 and FLT3/ITD had CR rate of 38% compared to that of 83% in patients with NUP98/NSD1 without FLT3/ITD. We also evaluated NUP98/NSD1 in patients treated on SWOG 0106. Of the 595 patients enrolled (age >18 to <60 years), 133 with either CN-AML or FLT3/ITD had available diagnostic specimens for analysis. Within the FLT3/ITD cohort, 8.5% (5 out of 59) patients also harbored NUP98/NSD1. Four of these 5 patients failed to achieve CR; the only patient with dual FLT3/ITD and NUP98/NSD1 alteration who achieved CR, died within a year of relapsed AML. There was only 1 patient with CN-AML with NUP98/NSD1 who did not harbor FLT3/ITD. This was the only patient who achieved and remained alive at 4.5 years of follow-up. The CR rate among FLT3/ITD patients without NUP98/NSD1 was 69%. In this large cooperative study we demonstrated that NUP98/NSD1 is commonly seen in children and young adults with AML with high association with CN-AML and very high overlap with FLT3/ITD. Although the CR rate is not affected in those with FLT3/ITD, we demonstrated that those with dual FLT3/ITD and NUP98/NSD1 alterations have extremely low CR rate and high post-induction MRD than FLT3/ITD patients without NUP98/NSD1. In contrast, NUP98/NSD1 patients without FLT3/ITD have a more favorable CR rate and survival. Within FLT3/ITD patients, the presence of NUP98/NSD1 can be used to identify those at very high risk for induction failure. The high simultaneous frequency of NUP98/NSD1 and WT1 in FLT3/ITD AML suggests a cooperative mechanism among these genetic lesions into leukemogenesis. Targeted therapy strategies should be developed for this subgroup of patients with highly resistant disease. Disclosures: No relevant conflicts of interest to declare.

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Prognostic and therapeutic impacts of mutant TP53 variant allelic frequency in newly diagnosed acute myeloid leukemia

Blood Advances ◽

10.1182/bloodadvances.2020003120 ◽

2020 ◽

Vol 4 (22) ◽

pp. 5681-5689

Author(s):

Nicholas J. Short ◽

Guillermo Montalban-Bravo ◽

Hyunsoo Hwang ◽

Jing Ning ◽

Miguel J. Franquiz ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Allelic Frequency ◽

Prognostic Impact ◽

Newly Diagnosed ◽

Prognostic Information ◽

First Line Therapy ◽

Frontline Therapy ◽

The Impact ◽

Acute Myeloid

Abstract TP53 mutations are associated with poor outcomes in acute myeloid leukemia (AML). The prognostic impact of mutant TP53 (TP53mut) variant allelic frequency (VAF) is not well established, nor is how this information might guide optimal frontline therapy. We retrospectively analyzed 202 patients with newly diagnosed TP53-mutated AML who underwent first-line therapy with either a cytarabine- or hypomethylating agent (HMA)–based regimen. By multivariate analysis, TP53mut VAF >40% was independently associated with a significantly higher cumulative incidence of relapse (P = .003) and worse relapse-free survival (P = .001) and overall survival (OS; P = .003). The impact of TP53mut VAF on clinical outcomes was driven by patients treated with a cytarabine-based regimen (median OS, 4.7 vs 7.3 months for VAF >40% vs ≤40%; P = .006), whereas VAF did not significantly affect OS in patients treated with HMA. The addition of venetoclax to HMA did not significantly affect OS compared with HMA without venetoclax, both in the entire TP53-mutated population and in patients stratified by TP53mut VAF. Among patients with TP53mut VAF ≤40%, OS was superior in those treated with higher-dose cytarabine, whereas OS was similarly poor for patients with TP53mut VAF >40% regardless of therapy. The best long-term outcomes were observed in those with 1 TP53 mutation with VAF ≤40% who received a frontline cytarabine-based regimen (2-year OS, 38% vs 6% for all others; P < .001). In summary, TP53mut VAF provides important prognostic information that may be considered when selecting frontline therapy for patients with newly diagnosed TP53-mutated AML.

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