Title:New Strategies in the Chemotherapy of Leukemia: Eradicating Cancer Stem Cells in Chronic Myeloid Leukemia
Volume: 12
Issue: 5
Author(s): A. Stefanachi, F. Leonetti, O. Nicolotti, M. Catto, L. Pisani, S. Cellamare, C. Altomare and A. Carotti
Affiliation:
Keywords:
BCR-ABL, chronic myeloid leukemia, leukemic stem cells, tyrosine kinase inhibitors
Abstract: Chronic myeloid leukemia (CML) is a myeloproliferative disorder caused by the Philadelphia-positive
chromosome deriving from a translocation between chromosomes 22 and 9. The oncogenic product of this aberrant
chromosome is the constitutively active tyrosine kinase BCR-ABL that is responsible for leukemic cell growth,
proliferation and survival driven by the dysregulation of a large array of signal transduction pathways. Inhibition of BCRABL
with tyrosine kinase inhibitors proved to be an efficient therapy of CML in the chronic phase. Unfortunately, the
impressive success of BCR-ABL inhibitors as front-line therapy in CML has been tempered by problems of disease
persistence or relapse arising from different mechanisms, including mutations in the kinase domain of the enzyme BCRABL
and mechanisms independent from BCR-ABL activity. Growing evidence has also suggested a pivotal role of
persistent leukemic cancer stem cells, characterized by high self-renewal and pluripotency, in CML maintenance and/or
relapse. The present review deals with the most recent advances in this challenging field and focuses on the development
of new drugs and therapeutic approaches to eradicate the subtle and dangerous leukemic stem cells responsible for
maintaining and sustaining tumor growth.
