NRAS G12

While these emiPS cells remain transgene-dependent, we inactivated the transgenes and differentiated emiPS cells into all three germ layers via tri-lineage differentiation, embryoid body generation and direct differentiation into putative cell types from all three layers. These methods will open new frontiers for cellular models of nonmodel organisms, including for genetic rescue and conservation.

Anti-CD69 monoclonal antibody treatment was associated with reduced generation of granulocyte-macrophage progenitor cells, prolonged survival, and decreased Treg accumulation in the BME. Our findings suggest that CD69 may serve as a biomarker of BME immunological dysfunction in CMML.

P1, N=24, Recruiting, Ruijin Hospital

Mouse embryonic fibroblasts transformed with KRASG12C also contain more saturated lipids than KRASG12D MEFs. Thus, activities of KRAS mutants depends on lipid acyl chain remodeling in an allele-specific manner.

HRAS p.G13R induced strongest molecular changes suggesting most serious pathobiological consequences, and HRAS p.G12S and p.G12V predominantly interfered with cellular signaling. Taken together, our data underscore the existence of HRAS variant-specific qualities of dysregulation and describe a differential pathophysiological architecture of HRAS-associated phenotypes.

P=N/A, N=9, Terminated, University Hospital, Bordeaux | Completed --> Terminated; Target number of inclusion not reached

After ruxolitinib therapy, he later developed leukocytosis and 2% circulating blasts. Repeat marrow demonstrated ≥ 15% ring sideroblasts. Retrospectively, the initial biopsy fulfills ICC 2022 criteria for MDS/MPN-SF3B1-T, highlighting the diagnostic value of genetics-integrated classification in fibrotic marrows.

Moreover, FTY720 co-treatment resensitized G12D NRAS-mutated M14(R)701 cells to gilteritinib in vivo. Co-treatment inactivated ERK, transcriptionally downregulated SPHK1, and inactivated downstream AKT, p70 S6K and BAD, with inactivation abrogated by constitutive SPHK1 expression. The clinically applicable S1PR modulators fingolimod and mocravimod resensitize NRAS-mutated FLT3-ITD AML cells to FLT3 inhibitors, supporting potential clinical efficacy.

P3, N=590, Recruiting, Revolution Medicines, Inc. | N=420 --> 590

ProgEvo enabled inference of a molecular evolution model and integration of evolution-informed covariates into clinical prognostic frameworks, supporting the development of the IPSS-M-Evo model. A free web-based tool allows clinicians to calculate the IPSS-M-Evo score and match individual mutational profiles to cohort-derived evolutionary trajectories (https://evoclin.unimib.it/tools/evolution-graphs.html and https://evoclin.unimib.it/tools/ipssmevo.html). (Funded by the European Union and others.).

P1/2, N=5, Terminated, National Cancer Institute (NCI) | Completed --> Terminated; Study was closed due to lack of accrual and study outcomes overlapped with another protocol's eligibility.

P1, N=18, Not yet recruiting, Beijing DCTY Biotech Co.,Ltd. | N=110 --> 18 | Trial completion date: May 2028 --> Aug 2028 | Trial primary completion date: May 2028 --> Aug 2028