Juvenile myelomonocytic leukemia – A bona fide RASopathy syndrome

Terra Lasho, Mrinal M. Patnaik

Research output: Contribution to journalReview article

Abstract

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.

Original languageEnglish (US)
Article number101171
JournalBest Practice and Research: Clinical Haematology
DOIs
StateAccepted/In press - Jan 1 2020

Keywords

  • Juvenile myelomonocytic leukemia
  • RAS pathway mutations
  • RASopathy syndromes

ASJC Scopus subject areas

  • Oncology
  • Clinical Biochemistry

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