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Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Anti-proliferative evaluation of monoterpene derivatives against leukemia
Lekh Nath Gautam1, Taotao Ling1, Walter Lang1
1Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105-3678, USA.
Insights
Pediatric acute lymphoblastic leukemia (ALL) in infants with MLL-rearranged B-ALL has a poor survival rate. A novel phenolic compound shows potent anti-proliferative effects against these leukemia models.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Pediatric acute lymphoblastic leukemia (ALL) cure rates have improved, but high-risk groups like infants with MLL-rearranged (MLL-r) B-ALL still have poor outcomes (<35% survival).
- Current chemotherapy regimens are not effective for all patient cohorts, necessitating novel therapeutic strategies.
Purpose of the Study:
- To identify new molecular scaffolds for understanding MLL-r B-ALL mechanisms.
- To discover novel targeted treatments for high-risk pediatric leukemia.
Main Methods:
- Phenotypic screening was employed to identify promising chemical scaffolds.
- The anti-proliferative effects of a specific phenolic compound (Compound 31) were evaluated against human ALL leukemia cellular models.
Main Results:
- Phenolic natural products emerged as promising scaffolds from the initial screening.
- Compound 31 demonstrated potent anti-proliferative activity in human ALL leukemia cellular models.
Conclusions:
- Phenolic compounds represent a viable starting point for developing new anti-leukemia agents.
- Compound 31 warrants further investigation as a potential targeted therapy for MLL-r B-ALL.
Abstract:
The cure rate of pediatric acute lymphoblastic leukemia (ALL) has significantly improved in the past thirty years, however not all patient cohorts respond well to current chemotherapy regimens. Among the high risk patient cohort is infants with MLL-rearranged (MLL-r) B-ALL, which remains dismal with an overall survival rate <35%. Our program is interested in identifying new molecular scaffolds to better understand the underlying mechanisms and ultimately provide new targeted treatments. Based on a phenotypic screen, phenolic natural products were identified as promising scaffolds for further chemical evaluation. Herein we disclose the effects of a potent anti-proliferative compound 31 against human ALL leukemia cellular models.
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