The human FIP1L1 gene is located on chromosome 4 at position q12 (4q12), contains 19 exons, and codes for a complete protein consisting of 594 amino acids.

However, alternative splicing of its precursor mRNA results in multiple transcript variants encoding distinct FIP1L1 protein isoforms.

In consequence, they are highly stable, long-lived, unregulated, and continuously express the stimulating actions of their PDGFRA tyrosine kinase component.

[9] In consequence, cells expressing FIP1L1-PDGFRA fusion proteins differentiate and proliferate along eosinophil, other granulocyte, or T lymphocyte lineages and bearers of these mutations suffer either: a) chronic eosinophilia which may progress to hypereosinophilia, the hypereosinophilic syndrome, and chronic eosinophilic leukemia; b) a type of myeloproliferative neoplasm/myeloblastic leukemia not distinguished by eosinophilia; or c) T-lymphoblastic leukemia/lymphoma.

[9][10] The age-adjusted incidence of hypereosinophilic syndrome/chronic eosinophilic leukemia reported by the International Classification of Diseases for Oncology (Version 3) is ~0.036 per 100,000 with the mean frequency of FIP1L1-PDGFRA gene fusions occurring in ~10% of patients with hypereosinophilia as detected in developed countries.

[9][13][14] Patients expressing the eosinophil-driving fusion protein typically present with hypereosinophilia arbitrarily define as blood cell counts containing greater than 1.5x109/liter eosinophils that have persisted for more than 6 months.

Rather, definitive results are obtained by detecting the presence of the FIP1L1-PDGFRA fusion gene in the blood and/or bone marrow cells of sufferers by cytogenic analysis using fluorescence in situ hybridization or nested reverse transcription polymerase chain reaction testing.

Non-eosinophilic forms of FIP1L1-PDGFRA fusion gene-induced diseases are suggested by the presence of morphologically abnormal or excessive numbers of myeloid or lymphoid cells in the blood or bone marrow and, with respect to the lymphoid variants, by the presence of lymphadenopathy and/or lymphoma masses; ultimately, these variants also require demonstration of the FIP1L1-PDGFRA fusion genes for diagnosis.

Commonly, patients suffering this disease respond to low dos (e.g. 100 mg/day) Gleevec but if not attaining complete remission at this dose may require the higher dosages (up to 400/mg/day) typically used to treat CML.

While the success of Gleevec in treating the myeloproliferative neoplasm/myeloblastic leukemia or T-lymphoblastic leukemia/lymphoma forms of FIP1L1-PDGFRA fusion gene-induced disease is unclear, initial treatment with the drug is recommended.

Relatively little is known about function of or therapy for these translocations except that: a) the fusion gene was generated juxtaposing exons 15 and 3 of FIP1L1 and RARA, respectively; b) retinoic acid, a ligand for the RARA protein, is exceptionally potent in causing a human eosinophil line to die by apoptosis; c) the disease responses to retinoic acid as well as more aggressive therapies could not be evaluated because of severity and rapid progression of the diseases; d) and in vitro studies indicate that the FIP1L1-RARA fusion protein represses the activation of RARA-activated genes.