BCR-ABL1-induced leukemogenesis and autophagic targeting by arsenic trioxide

• Published in: Autophagy 2013-01, Vol.9 (1), p.93-94
• Main Authors: Goussetis, Dennis J., Gounaris, Elias, Platanias, Leonidas C.
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - pharmacology; arsenic trioxide; Arsenicals; Autophagic Punctum; autophagy; Autophagy - drug effects; Autophagy - physiology; BCR-ABL1; Binding; Biology; Bioscience; Calcium; Cancer; Cell; cell death; Cycle; Fusion Proteins, bcr-abl - metabolism; Humans; Landes; leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - metabolism; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Models, Biological; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Organogenesis; Oxides - toxicity; Proteins; Translational Medical Research
• ISSN: 1554-8627; 1554-8635
• DOI: 10.4161/auto.22259

We have recently shown that arsenic trioxide (As 2 O 3 ) is a potent inducer of autophagic degradation of the BCR-ABL1 oncoprotein, which is the cause of chronic myeloid leukemia (CML) and Ph+ acute lymphoid leukemia (Ph+ ALL). Our recently published work has shown that pharmacological inhibition of autophagy or molecularly targeting of elements of the autophagic machinery partially reverses the suppressive effects of As 2 O 3 on primitive leukemic precursors from CML patients. Altogether, our studies have provided direct evidence that arsenic-induced, autophagy-mediated, degradation of BCR-ABL1 is an important mechanism for the generation of the effects of As 2 O 3 on BCR-ABL1 transformed leukemic progenitors. These studies raise the potential of future clinical-translational efforts employing combinations of arsenic trioxide with autophagy-modulating agents to promote elimination of early leukemic progenitors and, possibly, leukemia-initiating stem cells.