ArticleLeukemia2019
Mutation-specific signaling profiles and kinase inhibitor sensitivities of juvenile myelomonocytic leukemia revealed by induced pluripotent stem cells.
Article in Leukemia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 50 citations in OpenAlex.
- Review
- Activity of trametinib as maintenance therapy after allogeneic hematopoietic stem cell transplantation in patients with relapsed or refractory RAS pathway-mutated hematologic malignancies.Annals of hematology · 2025Article
- Progression and perspectives in disease modeling for Juvenile myelomonocytic leukemia.Medical oncology (Northwood, London, England) · 2024Review
- LNK/Haematologica · 2024Article
- Review
- Leukemogenic SHP2 mutations lead to erythropoietin independency of HCD-57 cells: a novel model for preclinical research of SHP2-mutant JMML.Experimental hematology & oncology · 2023Article
- Using Pluripotent Stem Cells to Understand Normal and Leukemic Hematopoietic Development.Stem cells translational medicine · 2022Review
- Developing Bottom-Up Induced Pluripotent Stem Cell Derived Solid Tumor Models Using Precision Genome Editing Technologies.The CRISPR journal · 2022Review
- Increasing Complexity of Molecular Landscapes in Human Hematopoietic Stem and Progenitor Cells during Development and Aging.International journal of molecular sciences · 2022Review
- Review
- A retrospective analysis of azacitidine treatment for juvenile myelomonocytic leukemia.International journal of hematology · 2022Article
- Review
- Allogeneic Hematopoietic Stem Cell Transplantation for Mixed or Overlap Myelodysplastic/Myeloproliferative Disorders.Frontiers in oncology · 2022Review
- Molecular and phenotypic diversity of CBL-mutated juvenile myelomonocytic leukemia.Haematologica · 2022Article
- Review
- Review
- Current Treatment of Juvenile Myelomonocytic Leukemia.Journal of clinical medicine · 2021Review
- Treatment advances for pediatric and adult onset neoplasms with monocytosis.Current hematologic malignancy reports · 2021Review
- Induced pluripotent stem cell models of myeloid malignancies and clonal evolution.Stem cell research · 2021Review
- Great Expectations: Induced pluripotent stem cell technologies in neurodevelopmental impairments.International journal of medical sciences · 2021Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Juvenile myelomonocytic leukemia (JMML) is an uncommon myeloproliferative neoplasm driven by Ras pathway mutations and hyperactive Ras/MAPK signaling. Outcomes for many children with JMML remain dismal with current standard-of-care cytoreductive chemotherapy and hematopoietic stem cell transplantation. We used patient-derived induced pluripotent stem cells (iPSCs) to characterize the signaling profiles and potential therapeutic vulnerabilities of PTPN11-mutant and CBL-mutant JMML. We assessed whether MEK, JAK, and PI3K/mTOR kinase inhibitors (i) could inhibit myeloproliferation and aberrant signaling in iPSC-derived hematopoietic progenitors with PTPN11 E76K or CBL Y371H mutations. We detected constitutive Ras/MAPK and PI3K/mTOR signaling in PTPN11 and CBL iPSC-derived myeloid cells. Activated signaling and growth of PTPN11 iPSCs were preferentially inhibited in vitro by the MEKi PD0325901 and trametinib. Conversely, JAK/STAT signaling was selectively activated in CBL iPSCs and abrogated by the JAKi momelotinib and ruxolitinib. The PI3Kδi idelalisib and mTORi rapamycin inhibited signaling and myeloproliferation in both PTPN11 and CBL iPSCs. These findings demonstrate differential sensitivity of PTPN11 iPSCs to MEKi and of CBL iPSCs to JAKi, but similar sensitivity to PI3Ki and mTORi. Clinical investigation of mutation-specific kinase inhibitor therapies in children with JMML may be warranted.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.