Exploiting Clonal Evolution to Improve the Diagnosis and Treatment Efficacy Prediction in Pediatric AML

Bertuccio, Salvatore Nicola; Anselmi, Laura; Masetti, Riccardo; Lonetti, Annalisa; Cerasi, Sara; Polidori, Sara; Serravalle, Salvatore; Pession, Andrea

doi:10.3390/cancers13091995

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Exploiting Clonal Evolution to Improve the Diagnosis and Treatment Efficacy Prediction in Pediatric AML

Salvatore Nicola Bertuccio

^1,†,

^1,†,

^2,*

²,

²,

² and

Pediatric Oncology and Hematology “Lalla Seràgnoli”, Pediatric Unit-Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy

Pediatric Oncology and Hematology “Lalla Seràgnoli”, Pediatric Unit-IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy

Department of Biomedical and Neuromotor Sciences, University of Bologna, 40126 Bologna, Italy

Author to whom correspondence should be addressed.

^†

Co-First Authors.

Academic Editor: Katia Nones

Cancers 2021, 13(9), 1995; https://doi.org/10.3390/cancers13091995

Received: 17 March 2021 / Revised: 12 April 2021 / Accepted: 19 April 2021 / Published: 21 April 2021

(This article belongs to the Special Issue Next Generation Sequencing Application in Cancer Research)

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The use of innovative technologies has revolutionized cancer research in recent years, and in the field of pediatric oncohematology, great results have been achieved. However, within this context, acute myeloid leukemia still represents a considerable challenge for clinicians, as frequent cases of relapse or refractory disease, especially in specific subgroups, remain present. With this review, the authors aim to recapitulate the main features of this extremely heterogeneous malignancy, by highlighting the concept of clonal evolution and how, thanks also to the impact of new high throughput techniques, this could be exploited to deepen the current knowledge on molecular mechanisms driving this disease. Overall, this study will seek to pave the way for making new tools available to further improve diagnosis and treatment protocols in pediatric patients.

Abstract

Despite improvements in therapeutic protocols and in risk stratification, acute myeloid leukemia (AML) remains the leading cause of childhood leukemic mortality. Indeed, the overall survival accounts for ~70% but still ~30% of pediatric patients experience relapse, with poor response to conventional chemotherapy. Thus, there is an urgent need to improve diagnosis and treatment efficacy prediction in the context of this disease. Nowadays, in the era of high throughput techniques, AML has emerged as an extremely heterogeneous disease from a genetic point of view. Different subclones characterized by specific molecular profiles display different degrees of susceptibility to conventional treatments. In this review, we describe in detail this genetic heterogeneity of pediatric AML and how it is linked to relapse in terms of clonal evolution. We highlight some innovative tools to characterize minor subclones that could help to enhance diagnosis and a preclinical model suitable for drugs screening. The final ambition of research is represented by targeted therapy, which could improve the prognosis of pediatric AML patients, as well as to limit the side toxicity of current treatments. View Full-Text

Keywords: pediatric AML; NGS; clonal evolution; target therapy

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MDPI and ACS Style

Bertuccio, S.N.; Anselmi, L.; Masetti, R.; Lonetti, A.; Cerasi, S.; Polidori, S.; Serravalle, S.; Pession, A. Exploiting Clonal Evolution to Improve the Diagnosis and Treatment Efficacy Prediction in Pediatric AML. Cancers 2021, 13, 1995. https://doi.org/10.3390/cancers13091995

AMA Style

Bertuccio SN, Anselmi L, Masetti R, Lonetti A, Cerasi S, Polidori S, Serravalle S, Pession A. Exploiting Clonal Evolution to Improve the Diagnosis and Treatment Efficacy Prediction in Pediatric AML. Cancers. 2021; 13(9):1995. https://doi.org/10.3390/cancers13091995

Chicago/Turabian Style

Bertuccio, Salvatore N., Laura Anselmi, Riccardo Masetti, Annalisa Lonetti, Sara Cerasi, Sara Polidori, Salvatore Serravalle, and Andrea Pession. 2021. "Exploiting Clonal Evolution to Improve the Diagnosis and Treatment Efficacy Prediction in Pediatric AML" Cancers 13, no. 9: 1995. https://doi.org/10.3390/cancers13091995

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Exploiting Clonal Evolution to Improve the Diagnosis and Treatment Efficacy Prediction in Pediatric AML

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