^
    3d
    Neurofibromatosis type 1-associated tumors in children. (PubMed, Turk J Pediatr)
    The identification of patients with NF1 and their interittent follow-up are important for the early detection of potential complications, especially tumorigenesis. This review aimed to summarize NF1-associated tumors in pediatric patients and recently developed targeted therapies for treating these tumors.
    Review • Journal
    |
    NF1 (Neurofibromin 1)
    28d
    Novel humanized loss-of-function NF1 mouse model of juvenile myelomonocytic leukemia. (PubMed, Blood Adv)
    Importantly, NF1LOF cells displayed marked GM-CSF hypersensitivity in in vitro colony-forming unit assays - mirroring JMML; when transplanted into NSG-SGM3 mice, they caused rapid lethality, (median survival of 32 days), myeloid expansion, tissue infiltration (spleen, liver, and lungs), and specific upregulation of RAS/MAPK pathway and STAT5 genes, consistent with patient profiles. This first humanized NF1LOF mouse model recapitulates key JMML features, enabling investigation of disease mechanisms and targeted therapies.
    Preclinical • Journal
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    NF1 (Neurofibromin 1) • CSF2 (Colony stimulating factor 2)
    |
    RAS mutation
    1m
    ADVL1521: Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia (clinicaltrials.gov)
    P2, N=10, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2025 --> Oct 2026
    Trial completion date
    |
    NF1 (Neurofibromin 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11)
    |
    RAS mutation • CBL mutation
    |
    Mekinist (trametinib) • omipalisib (GSK2126458)
    2ms
    INCB 57643-103: Safety and Tolerability Study of INCB057643 in Participants With Myelofibrosis and Other Advanced Myeloid Neoplasms (clinicaltrials.gov)
    P1, N=140, Active, not recruiting, Incyte Corporation | Recruiting --> Active, not recruiting | N=231 --> 140
    Enrollment closed • Enrollment change
    |
    Jakafi (ruxolitinib) • INCB057643
    2ms
    Epigenetic risk stratification in juvenile myelomonocytic leukemia by targeted methylation analysis of the BMP4 locus. (PubMed, Clin Epigenetics)
    Specifically, the 20% of patients with highest BMP4 methylation had a 5-year DFS of 0.38, in contrast to 0.62 for the lowest 20% (p = 0.007). These findings highlight the potential of BMP4 methylation analysis as a complementary biomarker for JMML risk stratification, mirroring genome-wide methylation profiles known to associate with prognostic subgroups.
    Journal
    |
    PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • BMP4 (Bone Morphogenetic Protein 4)
    3ms
    The watch-and-wait approach for patients with juvenile myelomonocytic leukemia: results of the French cohort. (PubMed, Blood)
    These findings support W&W as a viable alternative in up to 30% of JMML patients, potentially sparing them from HSCT-associated risks. Given the persistence of clonal hematopoiesis and the risk of extra-hematological complications, long-term monitoring remains essential.
    Journal
    |
    NRAS (Neuroblastoma RAS viral oncogene homolog) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SH2B3 (SH2B Adaptor Protein 3)
    |
    NRAS mutation • CBL mutation
    3ms
    Clinical and molecular characterization of patients with juvenile myelomonocytic leukaemia. (PubMed, Br J Haematol)
    Mutational burden, cytogenetics and methylation subgrouping were combined to develop a risk stratification model that may help to prioritize patients for haematopoietic stem cell transplantation. In summary, advanced molecular testing is key to enabling an accurate diagnosis and predicting outcome in JMML.
    Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden)
    |
    RAS mutation
    3ms
    Two Cases of Juvenile Myelomonocytic Leukemia With Identical Somatic PTPN11 Mutations in Children After In Utero Exposure to Thiopurine-Containing Chemotherapy. (PubMed, Pediatr Blood Cancer)
    One mother underwent antileukemic treatment including thioguanine during early pregnancy; the other received 6-mercaptopurine for Crohn's disease throughout gestation. Each underwent allogeneic hematopoietic stem cell transplantation and is currently in remission. These findings suggest a possible link between prenatal thiopurine exposure and leukemogenesis.
    Journal
    |
    PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11)
    |
    mercaptopurine • thioguanine
    4ms
    Haploidentical Hematopoietic Stem Cell Transplantation With Ex Vivo TCR Alpha/Beta and CD19 Depletion in Pediatric Hematologic Malignancies (clinicaltrials.gov)
    P1, N=50, Recruiting, Washington University School of Medicine | N=32 --> 50 | Trial completion date: Nov 2027 --> May 2029 | Trial primary completion date: Nov 2027 --> May 2029
    Enrollment change • Trial completion date • Trial primary completion date
    |
    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • CD38 (CD38 Molecule) • CREBBP (CREB binding protein) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • AFF1 (AF4/FMR2 Family Member 1) • HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • HLA-DQB1 (Major Histocompatibility Complex, Class II, DQ Beta 1) • MECOM (MDS1 And EVI1 Complex Locus) • NCAM1 (Neural cell adhesion molecule 1) • NUP214 (Nucleoporin 214) • TCF3 (Transcription Factor 3) • FUS (FUS RNA Binding Protein) • HLA-B (Major Histocompatibility Complex, Class I, B) • KAT6A (Lysine Acetyltransferase 6A) • DEK (DEK Proto-Oncogene) • AFDN (Afadin, Adherens Junction Formation Factor) • EGR1 (Early Growth Response 1) • MLLT10 (MLLT10 Histone Lysine Methyltransferase DOT1L Cofactor)
    4ms
    The m6A methyltransferase METTL14 promotes oncogenic Kras induced juvenile myelomonocytic leukemia through dysregulating autophagy. (PubMed, Cell Death Differ)
    Finally, we observed that combined treatment with a m6A inhibitor and a MEK inhibitor synergistically suppressed JMML growth. Collectively, these findings highlight the critical role of METTL14 in JMML tumorigenesis and suggest that m6A modification represents a promising therapeutic target for this disease.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • METTL14 (Methyltransferase 14)
    |
    KRAS mutation • KRAS G12D • RAS mutation
    4ms
    LIN28B hypomethylation drives oncogenic signaling and stratifies poor prognosis in juvenile myelomonocytic leukemia. (PubMed, Transl Pediatr)
    LIN28B activation via promoter hypomethylation defines a high-risk JMML subgroup with cell cycle. Methylation-based stratification predicts survival, positioning LIN28B as a therapeutic target.
    Journal
    |
    PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • WT1 (WT1 Transcription Factor) • HEY1 (Hes Related Family BHLH Transcription Factor With YRPW Motif 1) • LIN28B (Lin-28 Homolog B)
    4ms
    Vorinostat Dose-escalation After Allogeneic Hematopoietic Cell Transplantation (clinicaltrials.gov)
    P1, N=15, Active, not recruiting, Johns Hopkins All Children's Hospital | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    azacitidine • Zolinza (vorinostat)