TY - JOUR
T1 - Juvenile myelomonocytic leukemia – A bona fide RASopathy syndrome
AU - Lasho, Terra
AU - Patnaik, Mrinal M.
N1 - Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/6
Y1 - 2020/6
N2 - Juvenile myelomonocytic leukemia (JMML) is a pediatric myelodysplastic/myeloproliferative neoplasm overlap syndrome with sustained peripheral blood monocytosis, aggressive features, and poor outcomes. In >90% of cases JMML is driven by germline or somatic mutations involving the canonical RAS pathway (PTPN11, NRAS, CBL, KRAS and NF1), with somatic mutations/alterations in RAS pathway genes (second hit), SETBP1, ASXL1 and JAK3 resulting in disease progression. While spontaneous regression has been seen in germline PTPN11 and CBL mutant JMML, in most patients, allogeneic stem cell transplant is the only curative modality. JMML shares several phenotypic features with its adult counterpart proliferative, chronic myelomonocytic leukemia (pCMML). pCMML largely occurs due to RAS pathway mutations that occur in the context of age related clonal hematopoiesis (TET2, SRSF2, ASXL1), while JMML is a bona fide RASopathy, with additional somatic mutations, including in epigenetic regulators genes resulting in disease progression.
AB - Juvenile myelomonocytic leukemia (JMML) is a pediatric myelodysplastic/myeloproliferative neoplasm overlap syndrome with sustained peripheral blood monocytosis, aggressive features, and poor outcomes. In >90% of cases JMML is driven by germline or somatic mutations involving the canonical RAS pathway (PTPN11, NRAS, CBL, KRAS and NF1), with somatic mutations/alterations in RAS pathway genes (second hit), SETBP1, ASXL1 and JAK3 resulting in disease progression. While spontaneous regression has been seen in germline PTPN11 and CBL mutant JMML, in most patients, allogeneic stem cell transplant is the only curative modality. JMML shares several phenotypic features with its adult counterpart proliferative, chronic myelomonocytic leukemia (pCMML). pCMML largely occurs due to RAS pathway mutations that occur in the context of age related clonal hematopoiesis (TET2, SRSF2, ASXL1), while JMML is a bona fide RASopathy, with additional somatic mutations, including in epigenetic regulators genes resulting in disease progression.
KW - Juvenile myelomonocytic leukemia
KW - RAS pathway mutations
KW - RASopathy syndromes
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U2 - 10.1016/j.beha.2020.101171
DO - 10.1016/j.beha.2020.101171
M3 - Review article
C2 - 32460983
AN - SCOPUS:85083881846
SN - 1521-6926
VL - 33
JO - Best Practice and Research: Clinical Haematology
JF - Best Practice and Research: Clinical Haematology
IS - 2
M1 - 101171
ER -