Dataset Information

Acute Myeloid Leukemia in Children: Emerging Paradigms in Genetics and New Approaches to Therapy.

ABSTRACT:

Purpose of review

Acute myeloid leukemia (AML) in children remains a challenging disease to cure with suboptimal outcomes particularly when compared to the more common lymphoid leukemias. Recent advances in the genetic characterization of AML have enhanced understanding of individualized patient risk, which has also led to the development of new therapeutic strategies. Here, we review key cytogenetic and molecular features of pediatric AML and how new therapies are being used to improve outcomes.

Recent findings

Recent studies have revealed an increasing number of mutations, including WT1, CBFA2T3-GLIS2, and KAT6A fusions, DEK-NUP214 and NUP98 fusions, and specific KMT2A rearrangements, which are associated with poor outcomes. However, outcomes are starting to improve with the addition of therapies such as gemtuzumab ozogamicin and FLT3 inhibitors, initially developed in adult AML. The combination of advanced risk stratification and ongoing improvements and innovations in treatment strategy will undoubtedly lead to better outcomes for children with AML.

SUBMITTER: Conneely SE

PROVIDER: S-EPMC7806552 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Acute Myeloid Leukemia in Children: Emerging Paradigms in Genetics and New Approaches to Therapy.

Conneely Shannon E SE Stevens Alexandra M AM

Current oncology reports 20210113 2

<h4>Purpose of review</h4>Acute myeloid leukemia (AML) in children remains a challenging disease to cure with suboptimal outcomes particularly when compared to the more common lymphoid leukemias. Recent advances in the genetic characterization of AML have enhanced understanding of individualized patient risk, which has also led to the development of new therapeutic strategies. Here, we review key cytogenetic and molecular features of pediatric AML and how new therapies are being used to improve ...[more]

PMID: 33439382

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Project description:Mutations in the fms-like tyrosine kinase 3 (FLT3) gene are detected in approximately one-third of patients with newly diagnosed acute myeloid leukemia (AML). These consist of the more common FLT3-internal tandem duplication (ITD) in approximately 20-25% of AML cases, and point mutations in the tyrosine kinase domain (TKD) in approximately 5-10%. FLT3 mutations, especially FLT3-ITD, are associated with proliferative disease, increased risk of relapse, and inferior overall survival when treated with conventional regimens. However, the recent development of well tolerated and active FLT3 inhibitors has significantly improved the outcomes of this aggressive subtype of AML. The multikinase inhibitor midostaurin was approved by the United States Food and Drug Administration (US FDA) in April 2017 for the frontline treatment of patients with FLT3-mutated (either ITD or TKD) AML in combination with induction chemotherapy, representing the first new drug approval in AML in nearly two decades. In November 2018, the US FDA also approved the second-generation FLT3 inhibitor gilteritinib as a single agent for patients with relapsed or refractory FLT3-mutated AML. Promising phase I and II efficacy data for quizartinib is likely to lead to a third regulatory approval in relapsed/refractory AML in the near future. However, despite the significant progress made in managing FLT3-mutated AML, many questions remain regarding the best approach to integrate these inhibitors into combination regimens, and also the optimal sequencing of different FLT3 inhibitors in various clinical settings. This review comprehensively examines the FLT3 inhibitors currently in clinical development, with an emphasis on their spectra of activity against different FLT3 mutations and other kinases, clinical safety and efficacy data, and their current and future roles in the management of AML. The mechanisms of resistance to FLT3 inhibitors and potential combination strategies to overcome such resistance pathways are also discussed.

Dataset Information

Acute Myeloid Leukemia in Children: Emerging Paradigms in Genetics and New Approaches to Therapy.

Purpose of review

Recent findings

Publications

Acute Myeloid Leukemia in Children: Emerging Paradigms in Genetics and New Approaches to Therapy.

Similar Datasets

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