Targeting sphingosine kinase 1 in acute myeloid leukemia: translation to clinic.

Acute myeloid leukemia (AML) is an aggressive heterogeneous group of malignancies resulting from various oncogenic genetic lesions that presents as an accumulation of immature myeloid cells in the bone marrow and peripheral blood. Standard induction chemotherapeutics have remained the front line therapy for AML for over 30 years, and despite being often highly effective at achieving initial disease remission, these responses are often short-lived resulting in relapse and death. Indeed, the overall survival in young adults ( < 60 years) is < 30% [1] . Unlike the ever-increasing repertoire of targeted therapies for lymphoproliferative disorders, currently all- trans-retinoic-acid represents the only targeted therapy in routine clinical use for the treatment of one subclass of AML, acute promyelocytic leukemia, with this approach yielding a more favorable prognosis in this AML subtype than presently achievable in any other form of AML. No targeted therapies are in routine clinical use for the remaining subtypes of AML, which constitute about 90% of all AML patients, and thus, there is an enormous unmet need to develop such targeted therapies.