NCCN Guidelines Insights: Acute Myeloid Leukemia, Version 2.2021

Pollyea, Daniel A.; Bixby, Dale; Perl, Alexander E.; Bhatt, Vijaya Raj; Altman, Jessica K.; Appelbaum, Frederick R.; Lima, Marcos de; Fathi, Amir T.; Foran, James M.; Gojo, Ivana; Hall, Aric C.; Jacoby, Meagan A.; Lancet, Jeffrey E.; Mannis, Gabriel N.; Marcucci, Guido; Martin, Michael; Mims, Alice S.; Neff, Jadee; Nejati, Reza; Olin, Rebecca L.; Percival, Mary Elizabeth; Prébet, Thomas; Przespolewski, Amanda; Rao, Dinesh S.; Ravandi‐Kashani, Farhad; Shami, Paul J.; Stone, Richard; Strickland, Stephen A.; Sweet, Kendra; Vachhani, Pankit; Wieduwilt, Matthew J.; Gregory, Kristina M.; Ogba, Ndiya; Tallman, Martin S.

doi:10.6004/jnccn.2021.0002

Cited by 225 publications

(216 citation statements)

References 54 publications

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“…AML is a heterogeneous disease with poor survival and a high relapse rate. With advances in understanding the pathogenesis of AML, novel potential therapies for AML, including the refinement of conventional cytotoxic chemotherapies, genetic and epigenetic targeted drugs, and immunotherapies, have been developed in recent years [ 17 , 18 , 19 ]. However, the treatment of AML with DNMT3A mutations still faces challenges.…”

Section: Introductionmentioning

confidence: 99%

DNMT3A Mutation-Induced CDK1 Overexpression Promotes Leukemogenesis by Modulating the Interaction between EZH2 and DNMT3A

et al. 2021

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DNMT3A mutations are frequently identified in acute myeloid leukemia (AML) and indicate poor prognosis. Previously, we found that the hotspot mutation DNMT3A R882H could upregulate CDK1 and induce AML in conditional knock-in mice. However, the mechanism by which CDK1 is involved in leukemogenesis of DNMT3A mutation-related AML, and whether CDK1 could be a therapeutic target, remains unclear. In this study, using fluorescence resonance energy transfer and immunoprecipitation analysis, we discovered that increased CDK1 could compete with EZH2 to bind to the PHD-like motif of DNMT3A, which may disturb the protein interaction between EZH2 and DNMT3A. Knockdown of CDK1 in OCI-AML3 cells with DNMT3A mutation markedly inhibited proliferation and induced apoptosis. CDK1 selective inhibitor CGP74514A (CGP) and the pan-CDK inhibitor flavopiridol (FLA) arrested OCI-AML3 cells in the G2/M phase, and induced cell apoptosis. CGP significantly increased CD163-positive cells. Moreover, the combined application of CDK1 inhibitor and traditional chemotherapy drugs synergistically inhibited proliferation and induced apoptosis of OCI-AML3 cells. In conclusion, this study highlights CDK1 overexpression as a pathogenic factor and a potential therapeutic target for DNMT3A mutation-related AML.

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Section: Introductionmentioning

confidence: 99%

DNMT3A Mutation-Induced CDK1 Overexpression Promotes Leukemogenesis by Modulating the Interaction between EZH2 and DNMT3A

et al. 2021

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“…The accumulation of blasts often causes high peripheral white cell counts and can also lead more rarely to the seeding of leukemic cells in extramedullary tissues (2). AML is a disease of the elderly, with a median age at presentation of over 65 (3). Remission induction treatment in AML consists of standard chemotherapy with a combination of cytarabine and daunorubicin generally followed by further consolidation chemotherapy and possibly a hematopoietic stem cell transplant according to patients risk profile.…”

Section: Introductionmentioning

confidence: 99%

The Role of Metabolism in the Development of Personalized Therapies in Acute Myeloid Leukemia

Dembitz

Gallipoli

2021

Front. Oncol.

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Despite significant recent advances in our understanding of the biology and genetics of acute myeloid leukemia (AML), current AML therapies are mostly based on a backbone of standard chemotherapy which has remained mostly unchanged for over 20 years. Several novel therapies, mostly targeting neomorphic/activating recurrent mutations found in AML patients, have only recently been approved following encouraging results, thus providing the first evidence of a more precise and personalized approach to AML therapy. Rewired metabolism has been described as a hallmark of cancer and substantial evidence of its role in AML establishment and maintenance has been recently accrued in preclinical models. Interestingly, unique metabolic changes are generated by specific AML recurrent mutations or in response to diverse AML therapies, thus creating actionable metabolic vulnerabilities in specific patient groups. In this review we will discuss the current evidence supporting a role for rewired metabolism in AML pathogenesis and how these metabolic changes can be leveraged to develop novel personalized therapies.

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“…Acute myeloid leukemias (AML) are a heterogenous group of malignant diseases of the blood characterized by clonal expansion of myeloblasts in the bone marrow (≥20%), in peripheral blood, and/or in other tissues [1]. AML is a rare disease and accounts for 1.1% of all malignant diseases.…”

Section: Introductionmentioning

confidence: 99%

“…diseminovana intravaskularna koagulopatija u akutnoj nepromijelocitnoj mijeloidnoj leukemiji učestalost, kliničko-laboratorijske karakteristike i prognostički značaj disseminated intravascular coagulopathy in non-promyelocytic acute myeloid leukemia incidence, clinical and laboratory features and prognostic significance UVOD Akutne mijeloidne leukemije (AML) su heterogena grupa malignih bolesti krvi koje karakteriše klonalna ekspanzija mijeloblasta u koštanoj srži (≥20%), perifernoj krvi i/ili drugim tkivima [1]. AML se ubraja u retke bolesti i čini 1,1% svih malignih bolesti.…”

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Disseminated intravascular coagulopathy in non-promyelocytic acute myeloid leukemia: Incidence, clinical and laboratory features and prognostic significance

Cvetković¹,

Mitrović²

2021

Srpski medicinski časopis Lekarske komore

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Introduction: Acute promyelocytic leukemia (APL) has the highest risk for overt disseminated intravascular coagulopathy (DIC), with reported incidence of DIC of up to 90%, as compared to 10-40% in other AML types. The influence of DIC on early death in non-APL AML patients has not been evaluated so far. Aim: The aim of our study was to analyze the incidence of DIC, its clinical and laboratory characteristics, and the impact on the survival and early death of patients with non-APL AML. Materials and methods: A total of 176 patients with non-APL AML, diagnosed and treated at the Clinic for Hematology of the Clinical Center of Serbia, between 2015 and 2020, were evaluated retrospectively. The diagnosis of DIC was made on the basis of ISTH (International Society on Thrombosis and Haemostasias) criteria. Results: The mean age of our patients was 53.8 ± 14.6 years, with 99/176 patients being men (56.2%). DIC was present in 74/176 patients (42.05%), who had a significant prevalence of the hemorrhagic syndrome (p = 0.01). The risk factors for overt DIC were the following: older age (p <0.01), comorbidities (p = 0.01), leukocytosis (p <0.001) and a high level of LDH (p <0.001). The FAB (French, American and British) type of non-APL AML, the cytogenetic risk group, and CD56 (cluster of differentiation) had no influence on overt DIC (p > 0.05). No difference was found in early mortality, outcome, and the survival of non-APL AML patients, with and without DIC (p > 0.05). Conclusion: Older age at diagnosis, comorbidities, leukocytosis, and high LDH concentrations are found to be adverse risk factors for overt DIC in non-APL AML patients. If treated promptly, with immediate, adequate and intensive use of blood derivates and components, DIC has no negative impact on early mortality, outcome, and survival.

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NCCN Guidelines Insights: Acute Myeloid Leukemia, Version 2.2021

Cited by 225 publications

References 54 publications

DNMT3A Mutation-Induced CDK1 Overexpression Promotes Leukemogenesis by Modulating the Interaction between EZH2 and DNMT3A

DNMT3A Mutation-Induced CDK1 Overexpression Promotes Leukemogenesis by Modulating the Interaction between EZH2 and DNMT3A

The Role of Metabolism in the Development of Personalized Therapies in Acute Myeloid Leukemia

Disseminated intravascular coagulopathy in non-promyelocytic acute myeloid leukemia: Incidence, clinical and laboratory features and prognostic significance

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