Article
Molecular landscape and validation of new genomic classification in 2668 adult AML patients: real life data from the PETHEMA registry
Author/s | Sargas, Claudia
Ayala, Rosa Larráyoz, María José Chillón, María Carmen Carrillo-Cruz, Estrella Bilbao-Sieyro, Cristina Pérez Simón, José Antonio Montesinos, Pau |
Department | Universidad de Sevilla. Instituto de Biomedicina de Sevilla (IBIS) Universidad de Sevilla. Departamento de Medicina |
Publication Date | 2023 |
Deposit Date | 2024-02-02 |
Published in |
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Abstract | Next–Generation Sequencing (NGS) implementation to perform accurate diagnosis in acute
myeloid leukemia (AML) represents a major challenge for molecular laboratories in terms of specialization, standardization, costs and ... Next–Generation Sequencing (NGS) implementation to perform accurate diagnosis in acute myeloid leukemia (AML) represents a major challenge for molecular laboratories in terms of specialization, standardization, costs and logistical support. In this context, the PETHEMA cooperative group has established the first nationwide diagnostic network of seven reference laboratories to provide standardized NGS studies for AML patients. Cross–validation (CV) rounds are regularly performed to ensure the quality of NGS studies and to keep updated clinically relevant genes recommended for NGS study. The molecular characterization of 2856 samples (1631 derived from the NGS–AML project; NCT03311815) with standardized NGS of consensus genes (ABL1, ASXL1, BRAF, CALR, CBL, CEBPA, CSF3R, DNMT3A, ETV6, EZH2, FLT3, GATA2, HRAS, IDH1, IDH2, JAK2, KIT, KRAS, MPL, NPM1, NRAS, PTPN11, RUNX1, SETBP1, SF3B1, SRSF2, TET2, TP53, U2AF1 and WT1) showed 97% of patients having at least one mutation. The mutational profile was highly variable according to moment of disease, age and sex, and several co–occurring and exclusion relations were detected. Molecular testing based on NGS allowed accurate diagnosis and reliable prognosis stratification of 954 AML patients according to new genomic classification proposed by Tazi et al. Novel molecular subgroups, such as mutated WT1 and mutations in at least two myelodysplasia–related genes, have been associated with an adverse prognosis in our cohort. In this way, the PETHEMA cooperative group efficiently provides an extensive molecular characterization for AML diagnosis and risk stratification, ensuring technical quality and equity in access to NGS studies. |
Funding agencies | Ministerio de Economía y Competitividad |Instituto de Salud Carlos III, España |
Project ID. | PI18/01340
PI19/00730 PI19/01518 FI19/00059 |
Citation | Sargas, C., Ayala, R., Larráyoz, M.J., Chillón, M.C., Carrillo-Cruz, E., Bilbao-Sieyro, C.,...,Montesinos, P. (2023). Molecular landscape and validation of new genomic classification in 2668 adult AML patients: real life data from the PETHEMA registry. CANCERS, 15 (2), 438. https://doi.org/10.3390/cancers15020438. |
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