PDE6G inhibits the expression of CD71 in erythroid progenitor cells through the PDE6G/BHLHE40/miR144-3p/CD71 pathway, leading to red cell production obstacles and ultimately causing anemia in myelofibrosis

Abstract

Myelofibrosis(MF) is a haematological malignancy. Most patients with MF will develop mild to moderate anemia. The MF-related anemia results from multifactorial factors. At present, the molecular mechanisms leading to MF-related anemia are still not fully understood. This study aimed to explore the role of PDE6G in MF-related anemia, verify its effect on the differentiation of erythroid progenitors, and reveal the molecular mechanism of action. This study examined PDE6G expression in bone marrow samples from Philadelphia chromosome-negative MPN and patients with MF without anemia, followed by mechanism studies using the HEL cell line (with JAK2V617F mutation) model and validation in human bone marrow specimens. We found that PDE6G expression was significantly higher in bone marrow samples from MF patients with anemia than in patients without anemia, and PDE6G inhibited the expression of CD71 in erythroid progenitors through the PDE6G/BHLHE40/miR-144-3p/CD71 pathway, leading to impaired erythroid production and ultimately myelofibrosis anemia. In conclusion, this study revealed the important mechanism of PDE6G in MF-related anemia, providing new ideas for research and treatment in this field, and is expected to provide a theoretical basis for the treatment of MF-related anemia.