Leukemia: beneficial actions of retinoids and rexinoids.
Acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia, is the prototype of a cancer that can be cured by differentiation therapy using combined retinoic acid (RA) and chemotherapy. Acute promyelocytic leukemia is caused by chromosomal translocations, which in the large majority of cases generate the prototypic promyelocytic leukemia-retinoic-acid receptor alpha (PML-RARalpha) an oncogenic fusion protein formed from the retinoic-acid receptor alpha and the so-called PML protein. The fusion protein leads to the deregulation of wild type PML and RARalpha function, thus inducing the differentiation block and an altered survival capacity of promyelocytes of affected patients. A plethora of studies have revealed molecular details that account for the oncogenic properties of acute promyelocytic leukemia fusion proteins and the events that contribute to the therapy-induced differentiation and apoptosis of patients' blasts. Illustrating the beneficial mechanisms of action of retinoids for acute promyelocytic leukemia patients this review goes on to discuss a plethora of recently recognized molecular paradigms by which retinoids and rexinoids, alone or in combination with other compounds, regulate growth, differentiation and apoptosis also in non-acute promyelocytic leukemia cells, highlighting their potential as drugs for cancer therapy and prevention.
Altucci
Lucia
L
Seconda Università degli studi di Napoli, Dipartimento di Patologia Generale, vico L. De Crecchio 7, 80138, Napoli, Italy. lucia.altucci@unina2.it
Wilhelm
Emmanuelle
E
Gronemeyer
Hinrich
H
D017209:Apoptosis; D002454:Cell Differentiation; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D008024:Ligands; D008954:Models, Biological; D017434:Protein Structure, Tertiary; D018168:Receptors, Retinoic Acid / Q000627:therapeutic use*; D047488:Retinoid X Receptors; D012176:Retinoids / Q000378:metabolism / Q000502:physiology / Q000627:therapeutic use*; D014157:Transcription Factors / Q000627:therapeutic use*
D008024:Ligands; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids; D014157:Transcription Factors