Open AccessAdvances in therapies for acute promyelocytic leukemia
Author(s) -
Kamimura Tomohiko,
Miyamoto Toshihiro,
Harada Mine,
Akashi Koichi
Publication year - 2011
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2011.02045.x
Subject(s) - acute promyelocytic leukemia , arsenic trioxide , leukemia , cytarabine , anthracycline , medicine , hematopoietic stem cell transplantation , oncology , cancer research , immunology , transplantation , retinoic acid , biology , cancer , breast cancer , gene , apoptosis , biochemistry
Acute promyelocytic leukemia (APL), a distinct subtype of acute myelogenous leukemia (AML), results from the arrest of the maturation of hematopoietic progenitors at the promyelocyte stage. It has been shown that APL is associated with a reciprocal chromosomal translocation, involving chromosomes 15 and 17, which fuses the gene encoding the retinoic acid receptor α ( RARα ) and the promyelocytic leukemia ( PML ) gene. The resultant PML‐RARα fusion protein plays a critical role in the pathogenesis of APL. Although there are many subtypes of AML, all are typically managed using a standard chemotherapy regimen of an anthracycline plus cytarabine arabinoside (CA). Despite high rates of complete remission following standard chemotherapy, most patients relapse and long‐term disease‐free survival is only 30–40%. The introduction of drugs such as all‐ trans retinoic acid (ATRA) that promote progenitor differentiation by directly inhibiting the PML‐RARα fusion protein has changed the treatment paradigm for APL and markedly improved patient survival. The purposes of the present review are to provide the latest results and future directions of clinical research into APL and to illustrate how new therapies, such as ATRA plus anthracycline‐based induction and consolidation therapy, risk‐adapted therapy, salvage therapy containing arsenic trioxide‐based regimens, and hematopoietic stem cell transplantation, have improved the treatment outcomes for APL patients. ( Cancer Sci 2011; 102: 1929–1937)