Lama4, encoding laminin α4, is a major receptor-binding chain of several laminins. Laminins are important components of the extracellular matrix, playing crucial roles in cell adhesion, migration, and tissue development. Lama4 is involved in maintaining the integrity and function of the extracellular matrix, which is essential for normal cellular activities in various tissues [1,3].

In gene-knockout mouse models, Lama4 deletion led to impaired hematopoiesis regeneration after irradiation-induced stress, accompanied by altered bone marrow niche composition and inflammation. In a transplantation-induced MLL-AF9 acute myeloid leukemia (AML) mouse model, Lama4-/-mice showed accelerated AML progression and relapse. Lama4-/-mesenchymal stem cells (MSCs) had molecular alterations, promoting AML stem cell proliferation and chemoresistance [1].

In other studies, in gastric cancer, high LAMA4 expression was related to higher histological state, poorer survival, and cisplatin resistance [2,3]. In pancreatic cancer, LAMA4 upregulation was associated with high liver metastasis potential and poor survival outcome [4]. In preeclampsia, downregulation of LAMA4 in extravillous trophoblasts inhibited their proliferation, migration, and invasion, and affected vascular factor expression [5].

In conclusion, Lama4 plays essential roles in normal hematopoiesis and is involved in the progression of diseases like AML, gastric cancer, pancreatic cancer, and preeclampsia. Gene-knockout mouse models have been instrumental in revealing these functions, offering potential therapeutic targets for these diseases.