De novo acute megakaryoblastic leukemia with p210 BCR/ABL and t(1;16) translocation but not t(9;22) Ph chromosome

Xiao, Min; Na, Zhang; Liu, Yanan; Li, Chunrui

doi:10.1186/1756-8722-4-45

Cited by 5 publications

(2 citation statements)

References 20 publications

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“…Among these compounds, homoharringtonine (compound 10 [15,16,17]), a known potent protein synthesis inhibitor already approved for clinical use by the United States Food and Drug Administration against chronic myeloid leukemia (CML) [18,19,20] was identified. It shows high potency in the pre-B ALL cell models (SUP-B15 and KOPN-8) in agreement with previous reports [21,22]. However, it was not clear whether cephalotaxine (compound 9 ) worked via the same mechanism as compound 10 .…”

Section: Resultssupporting

confidence: 84%

Cytostatic and Cytotoxic Natural Products against Cancer Cell Models

et al. 2019

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The increasing prevalence of drug resistant and/or high-risk cancers indicate further drug discovery research is required to improve patient outcome. This study outlines a simplified approach to identify lead compounds from natural products against several cancer cell lines, and provides the basis to better understand structure activity relationship of the natural product cephalotaxine. Using high-throughput screening, a natural product library containing fractions and pure compounds was interrogated for proliferation inhibition in acute lymphoblastic leukemia cellular models (SUP-B15 and KOPN-8). Initial hits were verified in control and counter screens, and those with EC50 values ranging from nanomolar to low micromolar were further characterized via mass spectrometry, NMR, and cytotoxicity measurements. Most of the active compounds were alkaloid natural products including cephalotaxine and homoharringtonine, which were validated as protein synthesis inhibitors with significant potency against several cancer cell lines. A generated BODIPY-cephalotaxine probe provides insight into the mode of action of cephalotaxine and further rationale for its weaker potency when compared to homoharringtonine. The steroidal natural products (ecdysone and muristerone A) also showed modest biological activity and protein synthesis inhibition. Altogether, these findings demonstrate that natural products continue to provide insight into structure and function of molecules with therapeutic potential against drug resistant cancer cell models.

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Section: Resultssupporting

confidence: 84%

Cytostatic and Cytotoxic Natural Products against Cancer Cell Models

et al. 2019

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“…290 Thirty-four myelodysplastic syndromes patients with MDS-RAEB and RAEB-T were recruited for a clinical trial of two regimens therapy of either HAA regimen or Idarubicin Ara-C (IA) regimen. On HAD induction chemotherapy, the patient achieved partial hematological remission.…”

Section: Other Clinical Applicationsmentioning

confidence: 99%

Cephalotaxus Alkaloids

Pérard-Viret

Quteishat

Alsalim

et al. 2017

The Alkaloids: Chemistry and Biology

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Cephalotaxus alkaloids represent a family of plant secondary metabolites known for 60 years. Significant activity against leukemia in mice was demonstrated for extracts of Cephalotaxus. Cephalotaxine (CET) (1), the major alkaloid of this series was isolated from Cephalotaxus drupacea species by Paudler in 1963. The subsequent discovery of promising antitumor activity among new Cephalotaxus derivatives reported by Chinese, Japanese, and American teams triggered extensive structure elucidation and biological studies in this family. The structural feature of this cephalotaxane family relies mainly on its tetracyclic alkaloid backbone, which comprises an azaspiranic 1-azaspiro[4.4]nonane unit (rings C and D) and a benzazepine ring system (rings A and B), which is linked by its C3 alcohol function to a chiral oxygenated side chain by a carboxylic function alpha to a tetrasubstituted carbon center. The botanical distribution of these alkaloids is limited to the Cephalotaxus genus (Cephalotaxaceae). The scope of biological activities of the Cephalotaxus alkaloids is mainly centered on the antileukemic activity of homoharringtonine (HHT) (2), which in particular demonstrated marked benefits in the treatment of orphan myeloid leukemia and was approved as soon as 2009 by European Medicine Agency and by US Food and Drug Administration in 2012. Its exact mechanism of action was partly elucidated and it was early recognized that HHT (2) inhibited protein synthesis at the level of the ribosome machinery. Interestingly, after a latency period of two decades, the topic of Cephalotaxus alkaloids reemerged as a prolific source of new natural structures. To date, more than 70 compounds have been identified and characterized. Synthetic studies also regained attention during the past two decades, and numerous methodologies were developed to access the first semisynthetic HHT (2) of high purity suitable for clinical studies, and then high grade enantiomerically pure CET (1), HHT (2), and analogs.

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Thrombocytosis

Lindsey

Tiu

2013

The Coagulation Consult

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De novo acute megakaryoblastic leukemia with p210 BCR/ABL and t(1;16) translocation but not t(9;22) Ph chromosome

Cited by 5 publications

References 20 publications

Cytostatic and Cytotoxic Natural Products against Cancer Cell Models

Cytostatic and Cytotoxic Natural Products against Cancer Cell Models

Cephalotaxus Alkaloids

Thrombocytosis

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