FIP1L1

The FIP1L1 gene provides instructions for making part of a protein complex named cleavage and polyadenylation specificity factor (CPSF). This complex of proteins plays an important role in processing molecules called messenger RNAs (mRNAs), which serve as the genetic blueprints for making proteins. The CPSF protein complex helps add a string of the RNA building block adenine to the mRNA, creating a polyadenine tail or poly(A) tail. The poly(A) tail is important for stability of the mRNA and for protein production from the blueprint.

PDGFRA-associated chronic eosinophilic leukemia - caused by mutations in the FIP1L1 gene

A deletion of genetic material from chromosome 4 brings together part of the FIP1L1 gene and part of another gene called PDGFRA, creating the FIP1L1-PDGFRA fusion gene. This mutation is a somatic mutation, which means it is acquired during a person's lifetime and is present only in certain cells. This fusion gene causes PDGFRA-associated chronic eosinophilic leukemia, which is a type of blood cell cancer characterized by an increased number of eosinophils, a type of white blood cell involved in allergic reactions.

The FIP1L1-PDGFRA protein produced from the fusion gene has the function of the normal PDGFRA protein, which stimulates signaling pathways inside the cell that control many important cellular processes, such as cell growth and division (proliferation) and cell survival. Unlike the normal PDGFRA protein, however, the FIP1L1-PDGFRA protein is constantly turned on (constitutively activated), which means the cells are always receiving signals to proliferate. When the FIP1L1-PDGFRA fusion gene occurs in blood cell precursors, the growth of eosinophils (and occasionally other blood cells) is poorly controlled, leading to PDGFRA-associated chronic eosinophilic leukemia. It is unclear why eosinophils are preferentially affected by this genetic change.