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Article: Novel treatment strategies for acute promyelocytic leukemia

TitleNovel treatment strategies for acute promyelocytic leukemia
Authors
Issue Date2001
Citation
Oncology Spectrums, 2001, v. 2 n. 9, p. 640-648 How to Cite?
AbstractAcute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia. It is characterized morphologically by the proliferation of abnormal promyelocytes, karyotypically by the t(15;17)(q22;q21), and molecularly by the reciprocal fusion of the promyelocytic leukemia (PML) gene on chromosome 15 and the retinoic receptor alpha (RARA) gene on chromosome 17. Clinically, APL is associated with coagulopathy, due to the release of tissue factor from the leukemic promyelocytes, which can lead to early mortality. APL is the first leukemia that can be treated with differentiation therapy. All-trans-retinoic acid (ATRA), in vitro and in vivo, induces terminal differentiation of the APL cells by targeting the PML/RARA fusion protein for degradation. Clinically, ATRA can induce complete remission (CR) in most patients with APL through in vivo differentiation of the leukemic blasts. Combined with anthracycline-containing chemotherapy, it is the best induction therapy for newly diagnosed APL, with a >90% remission rate. Consolidation chemotherapy is needed to achieve molecular remission, and current data indicate that low-dose maintenance chemotherapy reduces relapses. An overall cure rate of 75% can be expected with this treatment strategy. However, about 10-15% of APL patients will still relapse. Arsenic trioxide (As2O3) is an effective treatment for APL in relapse. As2O3 acts by a variety of molecular mechanisms, including degradation of the PML/RARA protein, and a collapse in the mitochondrial transmembrane potential leading to apoptosis. As2O3 induces a high CR rate, about 90%, in relapsed APL. Consolidation by further As2O3 therapy, chemotherapy, or stem cell transplantation is needed to achieve molecular remission and long-term survival. The optimal postremission therapy for As2O3-treated relapses is being defined by ongoing clinical trials. With the availability of ATRA for newly diagnosed patients and As2O3 for relapses, a high cure rate can be expected for most patients.
Persistent Identifierhttp://hdl.handle.net/10722/162547
ISSN
References

 

DC FieldValueLanguage
dc.contributor.authorKwong, YLen_US
dc.date.accessioned2012-09-05T05:20:58Z-
dc.date.available2012-09-05T05:20:58Z-
dc.date.issued2001en_US
dc.identifier.citationOncology Spectrums, 2001, v. 2 n. 9, p. 640-648en_US
dc.identifier.issn1532-8554en_US
dc.identifier.urihttp://hdl.handle.net/10722/162547-
dc.description.abstractAcute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia. It is characterized morphologically by the proliferation of abnormal promyelocytes, karyotypically by the t(15;17)(q22;q21), and molecularly by the reciprocal fusion of the promyelocytic leukemia (PML) gene on chromosome 15 and the retinoic receptor alpha (RARA) gene on chromosome 17. Clinically, APL is associated with coagulopathy, due to the release of tissue factor from the leukemic promyelocytes, which can lead to early mortality. APL is the first leukemia that can be treated with differentiation therapy. All-trans-retinoic acid (ATRA), in vitro and in vivo, induces terminal differentiation of the APL cells by targeting the PML/RARA fusion protein for degradation. Clinically, ATRA can induce complete remission (CR) in most patients with APL through in vivo differentiation of the leukemic blasts. Combined with anthracycline-containing chemotherapy, it is the best induction therapy for newly diagnosed APL, with a >90% remission rate. Consolidation chemotherapy is needed to achieve molecular remission, and current data indicate that low-dose maintenance chemotherapy reduces relapses. An overall cure rate of 75% can be expected with this treatment strategy. However, about 10-15% of APL patients will still relapse. Arsenic trioxide (As2O3) is an effective treatment for APL in relapse. As2O3 acts by a variety of molecular mechanisms, including degradation of the PML/RARA protein, and a collapse in the mitochondrial transmembrane potential leading to apoptosis. As2O3 induces a high CR rate, about 90%, in relapsed APL. Consolidation by further As2O3 therapy, chemotherapy, or stem cell transplantation is needed to achieve molecular remission and long-term survival. The optimal postremission therapy for As2O3-treated relapses is being defined by ongoing clinical trials. With the availability of ATRA for newly diagnosed patients and As2O3 for relapses, a high cure rate can be expected for most patients.en_US
dc.languageengen_US
dc.relation.ispartofOncology Spectrumsen_US
dc.titleNovel treatment strategies for acute promyelocytic leukemiaen_US
dc.typeArticleen_US
dc.identifier.emailKwong, YL:ylkwong@hku.hken_US
dc.identifier.authorityKwong, YL=rp00358en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.scopuseid_2-s2.0-0035698075en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0035698075&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume2en_US
dc.identifier.issue9en_US
dc.identifier.spage640en_US
dc.identifier.epage648en_US
dc.identifier.scopusauthoridKwong, YL=7102818954en_US

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