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Can I read Mutation-specific Signaling Profiles and Kinase Inhibitor Sensitivities of Juvenile Myelomonocytic Leukemia Revealed by Induced Pluripotent Stem Cells on EtoBox?
Mutation-specific Signaling Profiles and Kinase Inhibitor Sensitivities of Juvenile Myelomonocytic Leukemia Revealed by Induced Pluripotent Stem Cells by Tasian, Sarah K.; Casas, Jessica A.; Posocco, David; Gandre-Babbe, Shilpa; Gagne, Alyssa L.; Liang, Ge; Loh, Mignon L.; Weiss, Mitchell J.; French, Deborah L.; Chou, Stella T. is a Medicine article available to read on EtoBox.
What is Mutation-specific Signaling Profiles and Kinase Inhibitor Sensitivities of Juvenile Myelomonocytic Leukemia Revealed by Induced Pluripotent Stem Cells about?
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 s
Who reads Mutation-specific Signaling Profiles and Kinase Inhibitor Sensitivities of Juvenile Myelomonocytic Leukemia Revealed by Induced Pluripotent Stem Cells?
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- Author
- Tasian, Sarah K.; Casas, Jessica A.; Posocco, David; Gandre-Babbe, Shilpa; Gagne, Alyssa L.; Liang, Ge; Loh, Mignon L.; Weiss, Mitchell J.; French, Deborah L.; Chou, Stella T.
- Publisher
- Nature Publishing Group; Springer Science and Business Media LLC (ISSN 0887-6924)
- Published
- 2018
- Language
- EN
- Field
- Medicine (Health Sciences)