^
    6d
    Alpha/Beta T Cell and CD19+ B Cell Depletion in Allogeneic Stem Cell Transplantation in Patients With Malignant Diseases (clinicaltrials.gov)
    P2, N=20, Recruiting, University of Florida | Trial completion date: May 2027 --> May 2028 | Trial primary completion date: May 2026 --> May 2027
    Trial completion date • Trial primary completion date
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3 mutation • CBL mutation
    7d
    Therapeutic Targeting of IL-17A-Driven PTGS2/NLRP3 Inflammasome Activation in Juvenile Myelomonocytic Leukemia. (PubMed, Blood)
    In patient-derived xenograft models of PTPN11-mutant JMML, dual NLRP3/PTGS2 inhibition combined with MEK blockade most effectively reduced leukemic burden, decreased human CD45⁺ engraftment, and depleted leukemic CD34⁺CD38⁺ progenitors and GMPs while restoring MEP populations, resulting in significantly improved overall survival. Together, these findings establish IL-17A/PTGS2/NLRP3 signaling as a central driver of immune suppression and myeloid expansion in PTPN11-mutant JMML and highlight combinatorial anti-inflammatory targeting as a promising therapeutic strategy for this high-risk disease.
    Journal • IO biomarker
    |
    CD8 (cluster of differentiation 8) • CD38 (CD38 Molecule) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • CD34 (CD34 molecule) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • PTGS2 (Prostaglandin-Endoperoxide Synthase 2) • IL17A (Interleukin 17A) • IL1B (Interleukin 1, beta) • NLRP3 (NLR Family Pyrin Domain Containing 3) • PACERR (PTGS2 Antisense NFKB1 Complex-Mediated Expression Regulator RNA)
    9d
    Disseminated Juvenile Xanthogranuloma in an Infant Requiring Systemic Therapy: A Case Report. (PubMed, Cureus)
    Although the course is most often self-limiting, justifying an initial conservative approach, certain extensive forms may require systemic treatment. The dermatologist plays a central role in diagnosis, based on a combination of clinical, dermoscopic, histopathological, and immunohistochemical findings, and in the multidisciplinary decision-making regarding treatment.
    Journal
    |
    CD163 (CD163 Molecule) • CD34 (CD34 molecule) • CD68 (CD68 Molecule)
    14d
    Molecular Advances in Juvenile Myelomonocytic Leukemia and Associated RASopathy. (PubMed, Cancers (Basel))
    Both genotype and DNA methylation subclassification have been integrated into clinical decision-making, incorporating pretransplant azacitidine, watch-and-wait approaches for favorable-risk patients, and emerging targeted therapies including MEK inhibitors. This review synthesizes recent advances in understanding JMML as a bona fide RASopathy; provides a diagnostic algorithm, molecular landscapes, and prognostic models; and highlights opportunities for molecularly targeted therapeutic intervention.
    Review • Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NF1 (Neurofibromin 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SH2B3 (SH2B Adaptor Protein 3)
    |
    KRAS mutation • ROS1 fusion • CBL mutation
    |
    azacitidine
    1m
    The role of RAS mutations in leukemia progression, differentiation, and drug resistance. (PubMed, Leuk Res Rep)
    Ultimately, RAS mutations drive monocytic differentiation of LSCs and venetoclax (VEN) resistance through BCL-2 family rewiring. Beyond AML, they are hallmark genetic lesions in juvenile myelomonocytic leukemia (JMML) and present in 15%-20% of pediatric acute lymphoblastic leukemia (ALL) cases. Here, we propose a comprehensive pathogenic model and targeted therapeutic framework focusing on RAS, MCL-1, BCL2L1 to overcome drug resistance and improve patient outcomes.
    Review • Journal • IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • BCL2L1 (BCL2-like 1) • RAS (Rat Sarcoma Virus) • CEBPA (CCAAT Enhancer Binding Protein Alpha)
    |
    KRAS mutation • NRAS mutation • FLT3-ITD mutation • KIT mutation • RUNX1 mutation • RAS mutation • MLL rearrangement • MLL mutation
    |
    Venclexta (venetoclax)
    1m
    EWOG MDS 2006: Study for Epidemiology and Characterization of Myelodysplastic Syndromes (MDS) and Juvenile Myelomonocytic Leucemia (JMML) in Childhood (clinicaltrials.gov)
    P=N/A, N=260, Recruiting, University Hospital Freiburg | Active, not recruiting --> Recruiting | Trial completion date: Dec 2024 --> Dec 2027 | Trial primary completion date: Dec 2023 --> Dec 2027
    Enrollment open • Trial completion date • Trial primary completion date
    2ms
    A Study to Find the Highest Dose of Imetelstat in Combination With Fludarabine and Cytarabine for Patients With AML, MDS or JMML That Has Come Back or Does Not Respond to Therapy (clinicaltrials.gov)
    P1, N=36, Recruiting, Children's Oncology Group | Trial completion date: Jun 2026 --> Mar 2028 | Trial primary completion date: Jun 2026 --> Mar 2028
    Trial completion date • Trial primary completion date
    |
    NF1 (Neurofibromin 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11)
    |
    RAS mutation • CBL mutation
    |
    cytarabine • methotrexate • leucovorin calcium • fludarabine IV • Rytelo (imetelstat) • Starasid (cytarabine ocfosfate)
    2ms
    Clinical and Genetic Characterization of Noonan Syndrome in a Colombian Pediatric Cohort. (PubMed, J Clin Res Pediatr Endocrinol)
    These findings underscore the genetic heterogeneity of NS and emphasize the importance of early molecular diagnosis to guide clinical management. Multidisciplinary follow-up is essential due to the risks of growth failure, cardiac anomalies, and malignancies.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • NF1 (Neurofibromin 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • LZTR1 (Leucine Zipper Like Transcription Regulator 1)
    2ms
    Successful Haplo-Hematopoietic Stem Cell Transplantation for Juvenile Myelomonocytic Leukemia in a Child With Underlying Thrombocytopenia-Absent Radius Syndrome: A Unique Case. (PubMed, Cancer Rep (Hoboken))
    This case represents, to our knowledge, one of the very few-if not the first-reported instances of successful HSCT for JMML in a patient with TAR syndrome. It underscores the importance of vigilant surveillance in TAR patients for potential malignant transformation and demonstrates the curative potential of HSCT in rare congenital-hematologic overlap syndromes.
    Journal
    |
    NF1 (Neurofibromin 1) • RBM8A (RNA Binding Motif Protein 8A)
    |
    RAS mutation
    |
    cyclophosphamide • melphalan • Grafapex (treosulfan)
    3ms
    US Study of ECT-001-CB in Pediatric and Young Adult Patients With High-Risk Myeloid Malignancies (clinicaltrials.gov)
    P1/2, N=13, Completed, ExCellThera inc. | Recruiting --> Completed | Trial completion date: Jun 2027 --> Dec 2025 | Trial primary completion date: Jun 2026 --> Dec 2025
    Trial completion • Trial completion date • Trial primary completion date
    |
    HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1) • CD34 (CD34 molecule)
    |
    cyclophosphamide • clofarabine • fludarabine IV • thiotepa • busulfan • Zemcelpro (dorocubicel)
    3ms
    SL03-OHD-104: Phase 1 Study of Shattuck Labs (SL)-172154 in Subjects With MDS or AML (clinicaltrials.gov)
    P1, N=106, Terminated, Shattuck Labs, Inc. | Completed --> Terminated; Development discontinued
    Trial termination
    |
    TP53 (Tumor protein P53)
    |
    TP53 mutation
    |
    Venclexta (venetoclax) • azacitidine • SL-172154
    3ms
    HAP2HCT: TCRαβ-depleted Progenitor Cell Graft With Additional Memory T-cell DLI, Plus Selected Use of Blinatumomab, in Naive T-cell Depleted Haploidentical Donor Hematopoietc Cell Transplantation for Hematologic Malignancies (clinicaltrials.gov)
    P2, N=69, Active, not recruiting, St. Jude Children's Research Hospital | N=140 --> 69 | Trial completion date: Aug 2025 --> Jun 2026
    Enrollment change • Trial completion date
    |
    FLT3 (Fms-related tyrosine kinase 3) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • ETV6 (ETS Variant Transcription Factor 6) • WT1 (WT1 Transcription Factor) • CREBBP (CREB binding protein) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • HOXA9 (Homeobox A9) • NUP214 (Nucleoporin 214) • CBFA2T3 (CBFA2/RUNX1 Partner Transcriptional Co-Repressor 3) • GLIS2 (GLIS Family Zinc Finger 2) • KAT6A (Lysine Acetyltransferase 6A) • KDM5A (Lysine Demethylase 5A) • DEK (DEK Proto-Oncogene) • AFDN (Afadin, Adherens Junction Formation Factor) • MLLT10 (MLLT10 Histone Lysine Methyltransferase DOT1L Cofactor)
    |
    FLT3-ITD mutation
    |
    cyclophosphamide • Blincyto (blinatumomab) • melphalan • fludarabine IV • mesna • thiotepa • Neupogen (filgrastim)