Novel Molecular Therapies and Genetic Landscape in Selected Rare Diseases with Hematologic Manifestations: A Review of the Literature.

Rare diseases affect less than 1 in 2000 people and are characterized by a serious, chronic, and progressive course. Among the described diseases, a mutation in a single gene caused mastocytosis, thrombotic thrombocytopenic purpura, Gaucher disease, and paroxysmal nocturnal hemoglobinuria ( KIT , ADAMTS13 , GBA1 , and PIG-A genes, respectively). In Castleman disease, improper ETS1 , PTPN6 , TGFBR2 , DNMT3A , and PDGFRB genes cause the appearance of symptoms. In histiocytosis, several mutation variants are described: BRAF , MAP2K1 , MAP3K1 , ARAF , ERBB3 , NRAS , KRAS , PICK1 , PIK3R2 , and PIK3CA . Genes like HPLH1 , PRF1 , UNC13D , STX11 , STXBP2 , SH2D1A , BIRC4 , ITK , CD27 , MAGT1 , LYST , AP3B1 , and RAB27A are possible reasons for hemophagocytic lymphohistiocytosis. Among novel molecular medicines, tyrosine kinase inhibitors, mTOR inhibitors, BRAF inhibitors, interleukin 1 or 6 receptor antagonists, monoclonal antibodies, and JAK inhibitors are examples of drugs expanding therapeutic possibilities. An explanation of the molecular basis of rare diseases might lead to a better understanding of the pathogenesis and prognosis of the disease and may allow for the development of new molecularly targeted therapies.