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Review
. 2015 Jan 9;4(1):127-49.
doi: 10.3390/jcm4010127.

Pediatric AML: From Biology to Clinical Management

Jasmijn D E de Rooij  1 , C Michel Zwaan  2 , Marry van den Heuvel-Eibrink  3
Affiliations
Review

Pediatric AML: From Biology to Clinical Management

Jasmijn D E de Rooij et al. J Clin Med. .

Abstract

Pediatric acute myeloid leukemia (AML) represents 15%-20% of all pediatric acute leukemias. Survival rates have increased over the past few decades to ~70%, due to improved supportive care, optimized risk stratification and intensified chemotherapy. In most children, AML presents as a de novo entity, but in a minority, it is a secondary malignancy. The diagnostic classification of pediatric AML includes a combination of morphology, cytochemistry, immunophenotyping and molecular genetics. Outcome is mainly dependent on the initial response to treatment and molecular and cytogenetic aberrations. Treatment consists of a combination of intensive anthracycline- and cytarabine-containing chemotherapy and stem cell transplantation in selected genetic high-risk cases or slow responders. In general, ~30% of all pediatric AML patients will suffer from relapse, whereas 5%-10% of the patients will die due to disease complications or the side-effects of the treatment. Targeted therapy may enhance anti-leukemic efficacy and minimize treatment-related morbidity and mortality, but requires detailed knowledge of the genetic abnormalities and aberrant pathways involved in leukemogenesis. These efforts towards future personalized therapy in a rare disease, such as pediatric AML, require intensive international collaboration in order to enhance the survival rates of pediatric AML, while aiming to reduce long-term toxicity.

Keywords: clinical management; cytogenetics; molecular aberrations; pediatric AML.

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Figures

Figure 1
Figure 1
Distribution of Type I/II abnormalities in pediatric AML. (A) Cooperating Type I and Type II mutations in pediatric AML. The circos plot [73] depicts the frequency of the Type II mutations and co-occurrence of Type I mutations in patients with de novo pediatric AML. The length of the arch corresponds to the frequency of the Type II mutation and the width of the ribbon with the percentage of patients with a specific Type I mutation or a combination of Type I mutations. FLT3/ITD denotes FLT3 internal tandem duplication; (B) Cooperating Type I and Type II mutations in cytogenetically normal AML. The circos plot [73] depicts the frequency of the Type II mutations and co-occurrence of Type I mutations in patients with de novo pediatric cytogenetically normal AML. The length of the arch corresponds to the frequency of the Type II mutation, and the width of the ribbon with the percentage of patients with a specific Type I mutation or a combination of Type I mutations. FLT3/ITD denotes FLT3 internal tandem duplication.
Figure 1
Figure 1
Distribution of Type I/II abnormalities in pediatric AML. (A) Cooperating Type I and Type II mutations in pediatric AML. The circos plot [73] depicts the frequency of the Type II mutations and co-occurrence of Type I mutations in patients with de novo pediatric AML. The length of the arch corresponds to the frequency of the Type II mutation and the width of the ribbon with the percentage of patients with a specific Type I mutation or a combination of Type I mutations. FLT3/ITD denotes FLT3 internal tandem duplication; (B) Cooperating Type I and Type II mutations in cytogenetically normal AML. The circos plot [73] depicts the frequency of the Type II mutations and co-occurrence of Type I mutations in patients with de novo pediatric cytogenetically normal AML. The length of the arch corresponds to the frequency of the Type II mutation, and the width of the ribbon with the percentage of patients with a specific Type I mutation or a combination of Type I mutations. FLT3/ITD denotes FLT3 internal tandem duplication.
Figure 2
Figure 2
Model of cooperating genetic events in AML. Different types of genetic and epigenetic events collaborate in leukemogenesis.
See this image and copyright information in PMC

References

    1. Howlader N.N.A., Krapcho M., Garshell J., Miller D., Altekruse S.F., Kosary C.L., Yu M., Ruhl J., Tatalovich Z., Mariotto A., et al. SEER Cancer Statistics Review, 1975–2011. National Cancer Institute; Bethesda, MD, USA: 2012.
    1. Seif A.E. Pediatric leukemia predisposition syndromes: Clues to understanding leukemogenesis. Cancer Genet. 2011;204:227–244. doi: 10.1016/j.cancergen.2011.04.005. - DOI - PubMed
    1. Tonnies H., Huber S., Kuhl J.S., Gerlach A., Ebell W., Neitzel H. Clonal chromosomal aberrations in bone marrow cells of Fanconi anemia patients: Gains of the chromosomal segment 3q26q29 as an adverse risk factor. Blood. 2003;101:3872–3874. doi: 10.1182/blood-2002-10-3243. - DOI - PubMed
    1. Hahn C.N., Chong C.E., Carmichael C.L., Wilkins E.J., Brautigan P.J., Li X.C., Babic M., Lin M., Carmagnac A., Lee Y.K., et al. Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia. Nat. Genet. 2011;43:1012–1017. doi: 10.1038/ng.913. - DOI - PMC - PubMed
    1. Link D.C., Schuettpelz L.G., Shen D., Wang J., Walter M.J., Kulkarni S., Payton J.E., Ivanovich J., Goodfellow P.J., Le Beau M., et al. Identification of a novel TP53 cancer susceptibility mutation through whole-genome sequencing of a patient with therapy-related AML. JAMA. 2011;305:1568–1576. doi: 10.1001/jama.2011.473. - DOI - PMC - PubMed

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