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Correction published on 9 July 2021, see Cancers 2021, 13(14), 3440.
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Review

Acute Promyelocytic Leukemia: A Constellation of Molecular Events around a Single PML-RARA Fusion Gene

1
Accredited Research Group in Hematology and Hemotherapy, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain
2
Department of Hematology, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain
3
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain
*
Author to whom correspondence should be addressed.
A.L. and M.I. contributed equally to this work.
Cancers 2020, 12(3), 624; https://doi.org/10.3390/cancers12030624
Submission received: 30 January 2020 / Revised: 27 February 2020 / Accepted: 5 March 2020 / Published: 8 March 2020
(This article belongs to the Special Issue Acute Promyelocytic Leukemia)

Abstract

Although acute promyelocytic leukemia (APL) is one of the most characterized forms of acute myeloid leukemia (AML), the molecular mechanisms involved in the development and progression of this disease are still a matter of study. APL is defined by the PML-RARA rearrangement as a consequence of the translocation t(15;17)(q24;q21). However, this abnormality alone is not able to trigger the whole leukemic phenotype and secondary cooperating events might contribute to APL pathogenesis. Additional somatic mutations are known to occur recurrently in several genes, such as FLT3, WT1, NRAS and KRAS, whereas mutations in other common AML genes are rarely detected, resulting in a different molecular profile compared to other AML subtypes. How this mutational spectrum, including point mutations in the PML-RARA fusion gene, could contribute to the 10%–15% of relapsed or resistant APL patients is still unknown. Moreover, due to the uncertain impact of additional mutations on prognosis, the identification of the APL-specific genetic lesion is still the only method recommended in the routine evaluation/screening at diagnosis and for minimal residual disease (MRD) assessment. However, the gene expression profile of genes, such as ID1, BAALC, ERG, and KMT2E, once combined with the molecular events, might improve future prognostic models, allowing us to predict clinical outcomes and to categorize APL patients in different risk subsets, as recently reported. In this review, we will focus on the molecular characterization of APL patients at diagnosis, relapse and resistance, in both children and adults. We will also describe different standardized molecular approaches to study MRD, including those recently developed. Finally, we will discuss how novel molecular findings can improve the management of this disease.
Keywords: acute promyelocytic leukemia; APL; NGS; minimal residual disease; MRD; PML-RARA; isoform; relapse; splicing acute promyelocytic leukemia; APL; NGS; minimal residual disease; MRD; PML-RARA; isoform; relapse; splicing

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MDPI and ACS Style

Liquori, A.; Ibañez, M.; Sargas, C.; Sanz, M.Á.; Barragán, E.; Cervera, J. Acute Promyelocytic Leukemia: A Constellation of Molecular Events around a Single PML-RARA Fusion Gene. Cancers 2020, 12, 624. https://doi.org/10.3390/cancers12030624

AMA Style

Liquori A, Ibañez M, Sargas C, Sanz MÁ, Barragán E, Cervera J. Acute Promyelocytic Leukemia: A Constellation of Molecular Events around a Single PML-RARA Fusion Gene. Cancers. 2020; 12(3):624. https://doi.org/10.3390/cancers12030624

Chicago/Turabian Style

Liquori, Alessandro, Mariam Ibañez, Claudia Sargas, Miguel Ángel Sanz, Eva Barragán, and José Cervera. 2020. "Acute Promyelocytic Leukemia: A Constellation of Molecular Events around a Single PML-RARA Fusion Gene" Cancers 12, no. 3: 624. https://doi.org/10.3390/cancers12030624

APA Style

Liquori, A., Ibañez, M., Sargas, C., Sanz, M. Á., Barragán, E., & Cervera, J. (2020). Acute Promyelocytic Leukemia: A Constellation of Molecular Events around a Single PML-RARA Fusion Gene. Cancers, 12(3), 624. https://doi.org/10.3390/cancers12030624

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