Unleashing the Guardian: The Targetable BCR-ABL/HAUSP/PML/PTEN Network in Chronic Myeloid Leukemia.
The complete eradication of Chronic Myeloid Leukemia is still challenging even in the era of highly selective and potent BCR-ABL tyrosine kinase inhibitors (TKIs). The 'Achilles heel' of TKI-based CML therapy is the inability of TKI to effectively target CML stem cells. Several pathways have been described to induce TKI insensitiveness in quiescent CML stem cells. In this review, we will describe the BCR-ABL/HAUSP/PML/PTEN network, whose signaling mediators converge to regulate the function of the tumor suppressor PTEN. We will also highlight the pharmacological strategies to modulate PTEN functions in order to sustain CML stem cell eradication.
Department of Clinical and Biological Sciences, University of Turin, regione Gonzole 10, 10043, Orbassano, Italy.
Alessandro
A
Morotti
Davide
D
Torti
Giovanna
G
Carra
Cristina
C
Panuzzo
Sabrina
S
Crivellaro
Riccardo
R
Taulli
Carmen
C
Fava
Angelo
A
Guerrasio
Giuseppe
G
Saglio
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D000071156:Promyelocytic Leukemia Protein / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D043222:Ubiquitin Thiolesterase / Q000235:genetics; D000076084:Ubiquitin-Specific Peptidase 7
D000970:Antineoplastic Agents; D000071156:Promyelocytic Leukemia Protein; C070576:PML protein, human; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C464569:USP7 protein, human; D043222:Ubiquitin Thiolesterase; D000076084:Ubiquitin-Specific Peptidase 7
BCR-ABL; HAUSP; PML; PTEN; chronic myeloid leukemia.