Pediatric Myeloproliferative neoplasms
2023-06-25 Sheng Xiao, MD , Chunxiao Yang Affiliation1.Brigham and Women's Hospital , Harvard Medical School, Boston , MA (USA)
2. Brigham and Women's Hospital, Harvard Medical School, Boston , MA (USA)
Classification
Definition
Pediatric Myeloproliferative neoplasms (pMPNs) are characterized by the increased production of one or more myeloid elements in peripheral blood and bone marrow. While most adult MPNs, including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PF), are rare in the pediatric population, with only a few case reports in the literature.1 Juvenile myelomonocytic leukemia (JMML) is a pediatric disease by definition. Chronic myeloid leukemia (CML) can be seen in children, with an incidence of 0.13 per 100,000 in those under 18 years of age.2
| Pediatric Myeloproliferative neoplasms | Genetic marker(s) |
|---|---|
| Chronic myeloid leukemia (CML) | The dominant driver gene of CML is the BCR::ABL1 fusion resulting from chromosome translation t(9;22)(q34;q11). Additional frequently mutated genes include ASXL1, DNMT3A, RUNX1, and TET2. All CML patients carry the BCR::ABL1, mostly from t(9;22), with a small number of cases from cytogenetic cryptic insertions.3 Three breakpoint clusters of the BCR genes include major-bcr, minor-bcr, and micro-bcr correlating to the p210, p190, and p230 BCR::ABL1 fusion proteins, respectively.4 Compared to adult CML, pediatric CML has a higher frequency of ASXL1 mutations.5 In addition, the BCR breakpoints in pediatric CML are similar to BCR::ABL1 positive acute lymphoblastic leukemia in adults (bimodal breakpoint distribution).4 |
| Juvenile myelomonocytic leukemia | Most JMML carries one of the five canonical RAS pathway mutations including PTPN11, NRAS, KRAS, NF1, and CBL.6 While PTPN11, NRAS or KRAS mutations are gain-of-function mutations, NF1 and CBL are tumor suppressors that are inactivatively mutated.7 Both NF1 and CBL mutations can be germline in origin and are seen in JMML in neurofibromatosis type 1 (NF1) and JMML in CBL mutation-associated syndrome (CBL syndrome).8 Additional mutations include second hits in one of the other RAS pathway genes (“RAS double mutants”), mutations in genes of the polycomb repressor complex (SETBP1, JAK3, SH2B3), or ASXL1, seen in less than half of the patients.9 Karyotype is typically normal, although monosomy 7 is observed in approximately 25% of the JMML, often seen in KRAS-mutated disease.10 JMMLs with PTPN11, NRAS, KRAS, or NF1 mutations require HSCT, however, CBL-mutated JMMLs are self-limiting in most patients.11 |
Article Bibliography
| Reference Number | Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|---|
| 1 | 32172359 | 2020 | Myeloproliferative Neoplasms in Children, Adolescents, and Young Adults. | Kucine N et al |
| 2 | 28410997 | 2017 | International incidence of childhood cancer, 2001-10: a population-based registry study. | Steliarova-Foucher E et al |
| 3 | 28404889 | 2017 | Cryptic BCR-ABL fusion gene as variant rearrangement in chronic myeloid leukemia: molecular cytogenetic characterization and influence on TKIs therapy. | Luatti S et al |
| 4 | 22887688 | 2012 | Genomic BCR-ABL1 breakpoints in pediatric chronic myeloid leukemia. | Krumbholz M et al |
| 5 | 35920965 | 2022 | Management of Chronic Myeloid Leukemia in Children and Young Adults. | Ford M et al |
| 6 | 26457647 | 2015 | The genomic landscape of juvenile myelomonocytic leukemia. | Stieglitz E et al |
| 7 | 30504325 | 2018 | JMML genomics and decisions. | Niemeyer CM et al |
| 8 | 34525182 | 2021 | Juvenile myelomonocytic leukemia in the molecular era: a clinician's guide to diagnosis, risk stratification, and treatment. | Wintering A et al |
| 9 | 31776464 | 2020 | Despite mutation acquisition in hematopoietic stem cells, JMML-propagating cells are not always restricted to this compartment. | Caye A et al |
| 10 | 33796386 | 2021 | Juvenile myelomonocytic leukemia-A comprehensive review and recent advances in management. | Gupta AK et al |
| 11 | 34300250 | 2021 | Current Treatment of Juvenile Myelomonocytic Leukemia. | Mayerhofer C et al |
Citation
Sheng Xiao, MD ; Chunxiao Yang
Pediatric Myeloproliferative neoplasms
Atlas Genet Cytogenet Oncol Haematol. 2023-06-25
Online version: http://atlasgeneticsoncology.org/solid-tumor/209173/pediatric-myeloproliferative-neoplasms
