Dataset Information

Advances in the pharmacological management of acute myeloid leukemia in adults.

ABSTRACT:

Introduction

With advances in molecular medicine and precision approaches, there has been significant improvement in the treatment of acute myeloid leukemia (AML) in recent years. This reflects better understanding of molecular and metabolic pathways in leukemia cells, including BCL2 upregulation that prevents apoptosis, FLT3 tyrosine kinase activating mutations that allow uncontrolled proliferation, and IDH mutations that result in differentiation block.

Areas covered

We performed a compressive review of important pre-clinical studies in AML that involve major molecular and metabolic pathways in AML, and we discussed standard therapeutic modalities and ongoing clinical trials for patients with AML, as well as an overall update of recent efforts in this area.

Expert opinion

Targeting these pathways has resulted in improvement in the overall survival of some groups of AML patients. Secondary AML and TP53 mutated AML remain challenging subtypes of AML with limited treatment options and represent areas of unmet research need. Ongoing work with menin inhibitors in MLL rearranged leukemia, which comprise a large portion of secondary AML cases, the development of CAR T cell products and targeting the CD47 receptor on macrophages in myeloid neoplasms including in TP53 mutated AML have provided hope for these challenging subtypes of AML.

SUBMITTER: Numan Y

PROVIDER: S-EPMC9648129 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Advances in the pharmacological management of acute myeloid leukemia in adults.

Numan Yazan Y Abaza Yasmin Y Altman Jessica K JK Platanias Leonidas C LC

Expert opinion on pharmacotherapy 20220907 13

<h4>Introduction</h4>With advances in molecular medicine and precision approaches, there has been significant improvement in the treatment of acute myeloid leukemia (AML) in recent years. This reflects better understanding of molecular and metabolic pathways in leukemia cells, including BCL2 upregulation that prevents apoptosis, FLT3 tyrosine kinase activating mutations that allow uncontrolled proliferation, and IDH mutations that result in differentiation block.<h4>Areas covered</h4>We performe ...[more]

PMID: 35938317

Similar Datasets

Project description:Acute myeloid leukemia (AML) is the most common acute leukemia in adults. While survival for younger patients over the last several decades has improved nearly sixfold with the optimization of intensive induction chemotherapy and allogeneic stem cell transplantation (alloHSCT), this effect has been largely mitigated in older and less fit patients as well as those with adverse-risk disease characteristics. However, the last 10 years has been marked by major advances in the molecular profiling of AML characterized by a deeper understanding of disease pathobiology and therapeutic vulnerabilities. In this regard, the classification of AML subtypes has recently evolved from a morphologic to a molecular and genetic basis, reflected by recent updates from the World Health Organization and the new International Consensus Classification system. After years of stagnation in new drug approvals for AML, there has been a rapid expansion of the armamentarium against this disease since 2017. Low-intensity induction therapy with hypomethylating agents and venetoclax has substantially improved outcomes, including in those previously considered to have a poor prognosis. Furthermore, targeted oral therapies against driver mutations in AML have been added to the repertoire. But with an accelerated increase in treatment options, several questions arise such as how to best sequence therapy, how to combine therapies, and if there is a role for maintenance therapy in those who achieve remission and cannot undergo alloHSCT. Moreover, certain subtypes of AML, such as those with TP53 mutations, still have dismal outcomes despite these recent advances, underscoring an ongoing unmet need and opportunity for translational advances. In this review, we will discuss recent updates in the classification and risk stratification of AML, explore the literature regarding low-intensity and novel oral combination therapies, and briefly highlight investigative agents currently in early clinical development for high-risk disease subtypes.

Dataset Information

Advances in the pharmacological management of acute myeloid leukemia in adults.

Introduction

Areas covered

Expert opinion

Publications

Advances in the pharmacological management of acute myeloid leukemia in adults.

Similar Datasets

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