Juvenile Myelomonocytic Leukemia (JMML)

Overview

Juvenile myelomonocytic leukemia (JMML) is a rare, aggressive myelodysplastic/myeloproliferative neoplasm of early childhood, classified under the MDS/MPN overlap category in OncoTree. It is characterized by clonal proliferation of myelomonocytic cells and is driven predominantly by RAS-pathway activating mutations (PTPN11, KRAS, NRAS, NF1, CBL). JMML carries a poor prognosis without hematopoietic stem cell transplantation.

Cohorts in the corpus

  • mixed_pipseq_2017 — PIPseq pediatric pan-cancer cohort (Columbia University Medical Center), which includes JMML cases among 101 high-risk pediatric patients PMID:28007021.

Recurrent alterations

  • PIPseq cohort: PTPN11 D61Y co-mutation with SETBP1 D868N reclassified one 4-year-old patient’s diagnosis from de novo AML to JMML (which subsequently evolved into AML); PTPN11 is a MEK-inhibitor target and the D61Y mutation activates RAS-MAPK signaling PMID:28007021.

Subtypes

  • JMML is driven by mutually exclusive RAS-pathway mutations; PTPN11-mutant cases can overlap with or evolve into AML.

Therapeutic landscape

  • MEK inhibitors are a candidate targeted therapy for RAS-pathway-mutant JMML; no matched targeted therapy was administered in the PIPseq case described PMID:28007021.

Sources

  • PMID:28007021 — Oberg et al. PIPseq pediatric pan-cancer sequencing program (n=101).

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