Genomic and Epigenomic Landscape of Juvenile Myelomonocytic Leukemia
Fiñana, Claudia (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Gómez Molina, Noel (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Alonso Moreno, Sandra (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Belver, Laura (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)

Fecha:	2022
Resumen:	Juvenile myelomonocytic leukemia (JMML) is a rare myelodysplastic/myeloproliferative neoplasm of early childhood. Most of JMML patients experience an aggressive clinical course of the disease and require hematopoietic stem cell transplantation, which is currently the only curative treatment. JMML is characterized by RAS signaling hyperactivation, which is mainly driven by mutations in one of five genes of the RAS pathway, including PTPN11, KRAS, NRAS, NF1, and CBL. These driving mutations define different disease subtypes with specific clinico-biological features. Secondary mutations affecting other genes inside and outside the RAS pathway contribute to JMML pathogenesis and are associated with a poorer prognosis. In addition to these genetic alterations, JMML commonly presents aberrant epigenetic profiles that strongly correlate with the clinical outcome of the patients. This observation led to the recent publication of an international JMML stratification consensus, which defines three JMML clinical groups based on DNA methylation status. Although the characterization of the genomic and epigenomic landscapes in JMML has significantly contributed to better understand the molecular mechanisms driving the disease, our knowledge on JMML origin, cell identity, and intratumor and interpatient heterogeneity is still scarce. The application of new single-cell sequencing technologies will be critical to address these questions in the future.
Ayudas:	Agencia Estatal de Investigación PID2020-117645RA-I00 Agencia Estatal de Investigación RYC2020-029400-I
Nota:	Fundació Carreras
Nota:	This work was supported by Spanish Ministry of Science and Innovation (PID2020-117645RB-I00/AEI/10.13039/501100011033 and RYC2020-029400-I/AEI/10.13039/501100011033), the FERO Foundation (BFero2020.03), and the Government of Andorra (ATC025-AND-2020). We thank the CERCA Program (Generalitat de Catalunya), the Josep Carreras Leukemia Research Institute and the Catalan Institute of Oncology for their institutional support. LB is supported by the Spanish Ministry of Science and Innovation (MCI) (PID2020-117645RB-I00/AEI/10.13039/501100011033 and RYC2020-029400-I/AEI/10.13039/501100011033), and the FERO Foundation (BFero2020.03). CF is supported by a PhD grant from the Government of Andorra (ATC025-AND-2020).
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Juvenile myelomonocytic leukemia ; RAS pathway ; DNA methylation ; Experimental therapeutics
Publicado en:	Cancers, Vol. 14 Núm. 5 (3-1 2022) , p. 1335, ISSN 2072-6694

DOI: 10.3390/cancers14051335
PMID: 35267643

20 p, 1.2 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Instituto de Investigación contra la Leucemia Josep Carreras
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