Systemic Notch downregulation promotes Kras G12D ‐induced myeloproliferative neoplasm

Hypothetical Atopic Dermatitis-Myeloproliferative Neoplasm Syndrome

Atopic dermatitis (AD) is a chronic inflammatory skin disease. Myeloproliferative neoplasms (MPNs) are hematopoietic malignancies caused by uncontrolled proliferation of hematopoietic stem/progenitor cells. Recent studies have described several mutant mice exhibiting both AD-like skin inflammation and MPN. Common pathways for skin inflammation encompass overexpression of thymic stromal lymphopo...

Low-dose methotrexate in myeloproliferative neoplasm models.

Nras(G12D/+) promotes leukemogenesis by aberrantly regulating hematopoietic stem cell functions.

Oncogenic NRAS mutations are frequently identified in human myeloid leukemias. In mice, expression of endogenous oncogenic Nras (Nras(G12D/+)) in hematopoietic cells leads to expansion of myeloid progenitors, increased long-term reconstitution of bone marrow cells, and a chronic myeloproliferative neoplasm (MPN). However, acute expression of Nras(G12D/+) in a pure C57BL/6 background does not in...

Oncogenic Kras promotes chemotherapy-induced growth factor shedding via ADAM17.

Oncogenic mutations in Kras occur in 40% to 45% of patients with advanced colorectal cancer (CRC). We have previously shown that chemotherapy acutely activates ADAM17, resulting in growth factor shedding, growth factor receptor activation, and drug resistance in CRC tumors. In this study, we examined the role of mutant Kras in regulating growth factor shedding and ADAM17 activity, using isogeni...

Disruption of STAT3 signalling promotes KRAS-induced lung tumorigenesis

STAT3 is considered to play an oncogenic role in several malignancies including lung cancer; consequently, targeting STAT3 is currently proposed as therapeutic intervention. Here we demonstrate that STAT3 plays an unexpected tumour-suppressive role in KRAS mutant lung adenocarcinoma (AC). Indeed, lung tissue-specific inactivation of Stat3 in mice results in increased Kras(G12D)-driven AC initia...