Philadelphia chromosome-negative myeloproliferative neoplasms: clinical aspects and treatment options.

Abstract

Clinical studies of Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) have progressed greatly with the discovery of mutations in three driver genes: JAK2, MPL, and calreticulin. Other genes that may play important roles in pathogenesis and progression of MPN have also been identified. Several prognostic prediction systems based on various risk factors including these genetic factors have been developed and utilized in clinical practice. All mutations of the three driver genes result in JAK2 activation, and JAK inhibitors have indeed improved clinical outcomes for primary myelofibrosis and polycythemia vera. However, they have minimal ability to inhibit clonogenic growth, far below that of ABL tyrosine kinase inhibitors in chronic myeloid leukemia. Therefore, hematopoietic stem cell transplantation (HSCT), which still has a high mortality rate, remains the only curative treatment for MPN. Efforts are being made to advance the treatment of MPN by refining HSCT methods, combining JAK inhibitors with other molecularly targeted agents, and reviewing the safety and clonogenic inhibitory effects of interferon-alfa.