title: New strategies in the chemotherapy of leukemia: eradicating cancer stem cells in chronic myeloid leukemia.
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 BCR-ABL 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.
authors.affiliation: Dipartimento Farma-cochimico, Università degli Studi di Bari Aldo Moro, via Orabona, 4, I- 70125, Bari, Italy. stefanachi@farmchim.uniba.it
authors.forename: A
authors.initials: A
authors.lastname: Stefanachi
authors.forename: F
authors.initials: F
authors.lastname: Leonetti
authors.forename: O
authors.initials: O
authors.lastname: Nicolotti
authors.forename: M
authors.initials: M
authors.lastname: Catto
authors.forename: L
authors.initials: L
authors.lastname: Pisani
authors.forename: S
authors.initials: S
authors.lastname: Cellamare
authors.forename: C
authors.initials: C
authors.lastname: Altomare
authors.forename: A
authors.initials: A
authors.lastname: Carotti
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016032:Randomized Controlled Trials as Topic
chemical_list: D000970:Antineoplastic Agents