LNK/SH2B3 Loss Exacerbates the Development of Myeloproliferative Neoplasms in CBL-deficient Mice.

ABSTRACT: Genetic variations of signaling modulator protein LNK (also called SH2B3) are associated with relatively mild myeloproliferative phenotypes in patients with myeloproliferative neoplasms (MPN). However, these variations can induce more severe MPN disease and even leukemic transformation when co-existing with other driver mutations. In addition to the most prevalent driver mutation JAK2V617F, LNK mutations have been clinically identified in patients harboring CBL inactivation mutations, but its significance remains unclear. Here, using a transgenic mouse model, we demonstrated that mice with the loss of both Lnk and Cbl exhibited severe splenomegaly, extramedullary hematopoiesis and exacerbated myeloproliferative characteristics. Moreover, a population of Mac1⁺ myeloid cells expre

SUBMITTER: Chen Y 

PROVIDER: S-EPMC11976319 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature