Arsenic-induced APL differentiation in cerebrospinal fluid

Helwig, Annett; Klemm, Matthias; Schüttig, Reinhard; Röllig, Christoph; Wassilew, Nasstasja; Ehninger, Gerhard; Illmer, Thomas

doi:10.1016/j.leukres.2006.06.011

Cited by 22 publications

(14 citation statements)

References 5 publications

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“…Fortunately, clinical data have demonstrated that ATO seems to be capable of crossing the blood-brain-barrier in humans [32,33,146,148,172]. In these patients treated with ATO, ATO concentrations in the cerebrospinal fluid were in the range of 12-30% compared with those in whole blood or plasma [33,146,172]. Furthermore, Meng et al have developed a non-invasive method via concomitant with 20% mannitol intravenous bolus injection to help ATO entering into central nervous system [173].…”

Section: Metabolism and Pharmacokineticsmentioning

confidence: 99%

Application of Arsenic Trioxide Therapy for Patients with Leukaemia

Yuan

Yoshino

Kaise

et al. 2010

Biological Chemistry of Arsenic, Antimony and Bismuth

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Section: Metabolism and Pharmacokineticsmentioning

confidence: 99%

Application of Arsenic Trioxide Therapy for Patients with Leukaemia

Yuan

Yoshino

Kaise

et al. 2010

Biological Chemistry of Arsenic, Antimony and Bismuth

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“…In this regard the concentration of arsenic trioxide determined in plasma of Trisenox®-treated promyelocytic leukaemia patients is in the range of 300 - 2900 nM [30,31], which is equal or tenfold higher than the IC 50 values for this compound in T. brucei (Table 1). In addition Trisenox® is not only detected in blood but also in cerebrospinal fluid [32]. Since the treatment of sleeping sickness is still problematic, and melarsoprol, one of the most prominent drugs used for late stage infections, has deadly side effects in about 5% of treated patients [33], the potential of Trisenox® as an alternative drug to treat sleeping should be explored.…”

Section: Discussionmentioning

confidence: 99%

Trypanosoma Brucei Aquaglyceroporins Facilitate the Uptake of Arsenite and Antimonite in a pH Dependent Way

Uzcátegui

Figarella²,

Bassarak

et al. 2013

Cell Physiol Biochem

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Background: Trypanosoma brucei is a primitive parasitic protozoan that thrives in diverse environments such as the midgut of the tsetse fly and the blood of a mammalian host. For an adequate adaptation to these environments, the parasite´s aquaglyceroporins play an important role. Methods and Results: In order to test their ability to transport trivalent arsenic and antimony, we expressed the three known Trypanosoma brucei aquaglyceroporins (TbAQPs) in the heterologous systems of yeast null aquaporin mutant and Xenopus laevis oocytes. For both expression systems, we found a pH dependent intracellular accumulation of As(III) or Sb(III) mediated by all of the three TbAQPs, with the exception of TbAQP1-As(III) uptake. Additionally, we observed that Trypanosoma brucei aquaglyceroporins allow the passage of As(III) in both directions. Conclusion: Taken together, these results demonstrated that T. brucei aquaglyceroporins can serve as entry routes for As(III) and Sb(III) into the parasitic cell, and that this uptake is pH sensitive. Therefore, aquaporins of protozoan parasites may be considered useful as a vehicle for drug delivery.

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“…In contrast, SAH did not occur in spite of ATO administration when CSF was free of APL cells [29]. Moreover, another article reported that significant levels of ATO (approximately 30 g/L, which is equivalent to approximately 400 nmol/L) [35] in the CSF was detected in a patient who received intravenous ATO and intrathecal chemotherapies for CNS relapse of APL [36]. In this patient, elevated leukocytes and induction of differentiation of APL cells in the CSF, mimicking the differentiation syndrome were observed during these therapies [36].…”

Section: Therapy With Ato For Cns Invasion Of Aplmentioning

confidence: 96%

“…Moreover, another article reported that significant levels of ATO (approximately 30 g/L, which is equivalent to approximately 400 nmol/L) [35] in the CSF was detected in a patient who received intravenous ATO and intrathecal chemotherapies for CNS relapse of APL [36]. In this patient, elevated leukocytes and induction of differentiation of APL cells in the CSF, mimicking the differentiation syndrome were observed during these therapies [36]. Because in primary APL samples, significant toxicity of ATO is observed at concentrations of 100-400 nmol/L, with approximately 50% cell death occurring at 500 nmol/L [37,38], these ATO levels in the CSF are considered to be in a therapeutic range.…”

Section: Therapy With Ato For Cns Invasion Of Aplmentioning

confidence: 99%

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

Nagai¹,

Takahashi²,

Kurokawa

2009

CNSNDDT

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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. These comprehensive understanding would be helpful for better management of patients with APL.

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Arsenic-induced APL differentiation in cerebrospinal fluid

Cited by 22 publications

References 5 publications

Application of Arsenic Trioxide Therapy for Patients with Leukaemia

Application of Arsenic Trioxide Therapy for Patients with Leukaemia

Trypanosoma Brucei Aquaglyceroporins Facilitate the Uptake of Arsenite and Antimonite in a pH Dependent Way

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

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