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Review
. 2022 Jun 18;27(12):3911.
doi: 10.3390/molecules27123911.

Molecular-Targeted Therapy of Pediatric Acute Myeloid Leukemia

Piotr Obszański  1 , Anna Kozłowska  1 , Jakub Wańcowiat  2 , Julia Twardowska  2 , Monika Lejman  3 , Joanna Zawitkowska  4
Affiliations
Review

Molecular-Targeted Therapy of Pediatric Acute Myeloid Leukemia

Piotr Obszański et al. Molecules. .

Abstract

Acute myeloid leukemia (AML) accounts for approximately 15-20% of all childhood leukemia cases. The overall survival of children with acute myeloid leukemia does not exceed 82%, and the 5-year event-free survival rates range from 46% to 69%. Such suboptimal outcomes are the result of numerous mutations and epigenetic changes occurring in this disease that adversely affect the susceptibility to treatment and relapse rate. We describe various molecular-targeted therapies that have been developed in recent years to meet these challenges and were or are currently being studied in clinical trials. First introduced in adult AML, novel forms of treatment are slowly beginning to change the therapeutic approach to pediatric AML. Despite promising results of clinical trials investigating new drugs, further clinical studies involving greater numbers of pediatric patients are still needed to improve the outcomes in childhood AML.

Keywords: acute myeloid leukemia; pediatric AML; target therapies.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Mechanism of action of the FLT3 and BCL−2 inhibitors. Midostaurin, gilteritinib and sorafenib by inhibiting the mutated type III receptor kinase cause the inhibition of STAT5 phosphorylation and deactivation of the Ras/Raf/MAPK and PI3K/Akt/mTOR pathways, suppressing tumor cell growth. Venetoclax binds to the BH3−binding groove of the BCL−2 protein. This causes the oligomerization and conformational change of BAX and BAK, leading to the formation of pores and mitochondrial outer membrane permeabilization, resulting in tumor cell death.
Figure 2
Figure 2
Mechanisms of action of epigenetic modifiers. Azacitidine and decitabine by inhibiting DNA methyltransferase reverse the aberrant hypermethylation of genes, which is a crucial epigenetic component of leukemic transformation. Pracinostat and panobinostat inhibit histone deacetylation, causing the re-expression of the genes involved in cell differentiation.
Figure 3
Figure 3
Place of novel AML therapies in the treatment algorithm. Target Therapies I include: Gemtuzumab ozogamicin, midostaurin, sorafenib, venetoclax, azacitidine, decitabine, panobinostat and CAR-T. Target Therapies II include: midostaurin, gilteritinib, venetoclax, azacitidine, decitabine, pracinostat, panobinostat and Camidanlumab tesrine.
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References

    1. Cancer Stat Facts: Leukemia—Acute Myeloid Leukemia (AML) [(accessed on 24 April 2022)]; Available online: https://seer.cancer.gov/statfacts/html/amyl.html.
    1. NCCR*Explorer: An Interactive Website for NCCR Cancer Statistics, National Cancer Institute. [(accessed on 24 April 2022)]; Available online: https://NCCRExplorer.ccdi.cancer.gov/
    1. Creutzig U., van den Heuvel-Eibrink M.M., Gibson B., Dworzak M.N., Adachi S., de Bont E., Harbott J., Hasle H., Johnston D., Kinoshita A., et al. Diagnosis and Management of Acute Myeloid Leukemia in Children and Adolescents: Recommendations from an International Expert Panel. Blood. 2012;120:3187–3205. doi: 10.1182/blood-2012-03-362608. - DOI - PubMed
    1. World Health Organization . WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. In: Swerdlow S.H., Campo E., Harris N.L., Jaffe E.S., Pileri S.A., Stein H., Thiele J., editors. World Health Organization Classification of Tumours. Revised 4th ed. International Agency for Research on Cancer; Lyon, France: 2017. pp. 129–173.
    1. Leukemia and Lymphoma Society. [(accessed on 26 April 2022)]. Available online: https://www.lls.org/leukemia/acute-myeloid-leukemia/diagnosis/aml-subtypes.