Biology, risk stratification, and therapy of pediatric acute leukemias: an update - PubMed (original) (raw)

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Biology, risk stratification, and therapy of pediatric acute leukemias: an update

Ching-Hon Pui et al. J Clin Oncol. 2011.

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Abstract

Purpose: We review recent advances in the biologic understanding and treatment of childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), identify therapeutically challenging subgroups, and suggest future directions of research.

Methods: A review of English literature on childhood acute leukemias from the past 5 years was performed.

Results: Contemporary treatments have resulted in 5-year event-free survival rates of approximately 80% for childhood ALL and almost 60% for pediatric AML. The advent of high-resolution genome-wide analyses has provided new insights into leukemogenesis and identified many novel subtypes of leukemia. Virtually all ALL and the vast majority of AML cases can be classified according to specific genetic abnormalities. Cooperative mutations involved in cell differentiation, cell cycle regulation, tumor suppression, drug responsiveness, and apoptosis have also been identified in many cases. The development of new formulations of existing drugs, molecularly targeted therapy, and immunotherapies promises to further advance the cure rates and improve quality of life of patients.

Conclusion: The application of new high-throughput sequencing techniques to define the complete DNA sequence of leukemia and host normal cells and the development of new agents targeted to leukemogenic pathways promise to further improve outcome in the coming decade.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.

Fig 1.

Estimated frequency of specific genotypes in childhood leukemias. (A) Genetic abnormalities in acute lymphoblastic leukemia (ALL). Data were modified from Pui et al by including recently identified genotypes. The genetic lesions that are exclusively seen in cases of T-cell ALL are indicated in purple. (B) Genetic abnormalities in acute myeloid leukemia (AML). Panel to the left demonstrates the most common karyotypic alterations. Eighty percent of all children have disease-associated genomic structural alterations. Mutation profile in those without cytogenetic abnormalities (normal karyotype) is shown in the right panel. Seventy-six percent of those in the normal karyotype population have one of the known mutations; thus, more than 95% of all children with AML have at least one known genomic abnormality. (With permission from Reaman and Smith).

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