Jak2 inhibitors: rationale and role as therapeutic agents in hematologic malignancies

Although the Jak2-V617F mutation has generated strong awareness because of its causative role in myeloproliferative disorders, reports of Jak2 gene aberrations linked to hematologic malignancies have preceded those of V617F by nearly a decade. These malignant mutations include Jak2 amino acid substitutions, deletions, insertions, and chromosomal translocations. As a consequence, researchers are increasingly focused on identifying Jak2 inhibitors that suppress aberrant Jak2 kinase activity. Some of these inhibitors may one day become therapeutically beneficial for individuals with Jak2-related hematologic malignancies. This review summarizes various Jak2 mutations associated with hematologic malignancies and assesses some of the Jak2 inhibitors in the preclinical phase or in clinical trials. By reviewing these specific areas, we hope to have a better understanding of Jak2's role in hematologic malignancies and to shed light on the utility of Jak2 inhibitors.