Beneficial and Adverse Effects of Molecularly Targeted Therapies for Acute Promyelocytic Leukemia in Central Nervous System

Author(s): Sumimasa Nagai, Tsuyoshi Takahashi, Mineo Kurokawa.

Journal Name: CNS & Neurological Disorders - Drug Targets

Volume 8 , Issue 5 , 2009

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Abstract:

Acute promyelocytic leukemia (APL) is a distinct subset of acute myeloid leukemia characterized by an abnormal fusion protein, PML/RARA. All-trans retinoic acid (ATRA) and arsenic trioxide, which are the major molecularly targeted therapies in APL, affect or degrade the PML/RARA fusion protein and cause differentiation and apoptosis of APL cells. These therapies have improved the prognosis of APL patients and are now the main therapeutic options in APL. In addition, gemtuzumab ozogamicin is another targeted therapy in APL. On the other hand, the prognosis of patients with central nervous system (CNS) relapses of APL remains poor. Therefore, CNS relapses have become major concerns, and effective therapeutic approaches for CNS relapses are needed. In fact, possible active roles of molecularly targeted therapies in CNS relapses of APL have been suggested, and several new approaches with molecularly targeted therapies for CNS relapses have been examined in APL. In this review, we discuss three main topics; the relationship between the incidence of CNS relapses and the introduction of molecularly targeted therapies for APL, new approaches with targeted therapies for CNS relapses of APL, and other complications of targeted therapies in CNS such as pseudotumor cerebri induced by ATRA and subarachnoid hemorrhage. This comprehensive understanding would be helpful for better management of patients with APL.

Keywords: Central nervous system, relapse, subarachnoid hemorrhage, acute promyelocytic leukemia, arsenic trioxide, alltrans retinoic acid, gemtuzumab ozogamicin, targeted therapy, pseudotumor cerebri

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Article Details

VOLUME: 8
ISSUE: 5
Year: 2009
Page: [387 - 392]
Pages: 6
DOI: 10.2174/187152709789541943
Price: $58

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