Genomic and Epigenomic Landscape of Juvenile Myelomonocytic Leukemia
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...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-03-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/14/5/1335 |
| _version_ | 1797475383167156224 |
|---|---|
| author | Claudia Fiñana Noel Gómez-Molina Sandra Alonso-Moreno Laura Belver |
| author_facet | Claudia Fiñana Noel Gómez-Molina Sandra Alonso-Moreno Laura Belver |
| author_sort | Claudia Fiñana |
| collection | DOAJ |
| description | 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 <i>PTPN11</i>, <i>KRAS</i>, <i>NRAS</i>, <i>NF1,</i> and <i>CBL</i>. 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. |
| first_indexed | 2024-03-09T20:44:22Z |
| format | Article |
| id | doaj.art-112e0851c1244530abce03b0ca3a6438 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T20:44:22Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-112e0851c1244530abce03b0ca3a64382023-11-23T22:49:26ZengMDPI AGCancers2072-66942022-03-01145133510.3390/cancers14051335Genomic and Epigenomic Landscape of Juvenile Myelomonocytic LeukemiaClaudia Fiñana0Noel Gómez-Molina1Sandra Alonso-Moreno2Laura Belver3Cancer and Leukemia Epigenetics and Biology Program, Josep Carreras Leukemia Research Institute (IJC), 08916 Badalona, Barcelona, SpainCancer and Leukemia Epigenetics and Biology Program, Josep Carreras Leukemia Research Institute (IJC), 08916 Badalona, Barcelona, SpainCancer and Leukemia Epigenetics and Biology Program, Josep Carreras Leukemia Research Institute (IJC), 08916 Badalona, Barcelona, SpainCancer and Leukemia Epigenetics and Biology Program, Josep Carreras Leukemia Research Institute (IJC), 08916 Badalona, Barcelona, SpainJuvenile 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 <i>PTPN11</i>, <i>KRAS</i>, <i>NRAS</i>, <i>NF1,</i> and <i>CBL</i>. 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.https://www.mdpi.com/2072-6694/14/5/1335juvenile myelomonocytic leukemiaRAS pathwayDNA methylationexperimental therapeutics |
| spellingShingle | Claudia Fiñana Noel Gómez-Molina Sandra Alonso-Moreno Laura Belver Genomic and Epigenomic Landscape of Juvenile Myelomonocytic Leukemia Cancers juvenile myelomonocytic leukemia RAS pathway DNA methylation experimental therapeutics |
| title | Genomic and Epigenomic Landscape of Juvenile Myelomonocytic Leukemia |
| title_full | Genomic and Epigenomic Landscape of Juvenile Myelomonocytic Leukemia |
| title_fullStr | Genomic and Epigenomic Landscape of Juvenile Myelomonocytic Leukemia |
| title_full_unstemmed | Genomic and Epigenomic Landscape of Juvenile Myelomonocytic Leukemia |
| title_short | Genomic and Epigenomic Landscape of Juvenile Myelomonocytic Leukemia |
| title_sort | genomic and epigenomic landscape of juvenile myelomonocytic leukemia |
| topic | juvenile myelomonocytic leukemia RAS pathway DNA methylation experimental therapeutics |
| url | https://www.mdpi.com/2072-6694/14/5/1335 |
| work_keys_str_mv | AT claudiafinana genomicandepigenomiclandscapeofjuvenilemyelomonocyticleukemia AT noelgomezmolina genomicandepigenomiclandscapeofjuvenilemyelomonocyticleukemia AT sandraalonsomoreno genomicandepigenomiclandscapeofjuvenilemyelomonocyticleukemia AT laurabelver genomicandepigenomiclandscapeofjuvenilemyelomonocyticleukemia |