The impact of molecularly targeted therapies upon the understanding of leukemogenesis and the role of hematopoietic stem cell transplantation in acute promyelocytic leukemia.
Acute promyelocytic leukemia (APL) is a distinct subset of acute myeloid leukemia. An abnormal fusion gene, PML/RARA is detected in approximately 98% of patients with APL. PML/RARA confers long-term self-renewal properties to promyelocytes. All-trans retinoic acid (ATRA) and arsenic trioxide (ATO), which are the major molecularly targeted therapies in APL, affect the PML/RARA fusion protein and cause differentiation and apoptosis of APL cells. Although the leukemia-initiating cells of APL may be present in a myeloid progenitor committed compartment, the precise population of those remains to be elucidated. However, recent studies have demonstrated the effect of ATRA and ATO on APL leukemia-initiating cells. Through these studies, we can understand more deeply how current clinical therapies lead to long-lasting remission of APL. ATRA and ATO have improved the prognosis of APL patients and have changed the role of hematopoietic stem cell transplantation (HSCT). At present, HSCT is not indicated for patients with APL in first complete remission, and considered for patients with relapsed APL. In this review, we discuss the three main topics as follows: the leukemia-initiating cells in APL, the current state-of-the-art treatment for newly diagnosed and relapsed APL, and the role of HSCT in APL patients.
Nagai
Sumimasa
S
Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Hongo, Bunkyo-ku, Tokio 1138655, Japan.
Takahashi
Tsuyoshi
T
Kurokawa
Mineo
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D005971:Glutamates / Q000627:therapeutic use*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics; D010087:Oxides / Q000627:therapeutic use*; D011355:Prodrugs / Q000627:therapeutic use*; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors / Q000235:genetics; D014212:Tretinoin / Q000627:therapeutic use*; D025521:Tumor Suppressor Proteins / Q000235:genetics
D001152:Arsenicals; D005971:Glutamates; D009687:Nuclear Proteins; D010087:Oxides; D011355:Prodrugs; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C546472:retinoyl glutamate; C070576:PML protein, human; D014212:Tretinoin; D000077237:Arsenic Trioxide