| Directed therapy for patients with myelodysplastic syndromes (MDS) by suppression of cyclin D1 with ON 01910.Na. | |
| | |
MedLine Citation:
|
PMID: 22524974 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND: We previously demonstrated upregulation of c-myc, survivin, and cyclin D1 in CD34+ bone marrow mononuclear cells (BMMNCs) of patients with trisomy 8 and monosomy 7 myelodysplastic syndromes (MDS). "Knockdown" of cyclin D1 by RNA interference decreased trisomy 8 cell growth, suggesting that this might be a therapeutic target in MDS. EXPERIMENTAL DESIGN: We performed preclinical studies using BMMNCs from patients with MDS and AML to examine the effects of the styryl sulfone ON 01910.Na on cyclin D1 accumulation, aneuploidy, and CD34+ blast percentage. We next treated twelve patients with higher risk MDS and two trisomy 8 AML patients with ON 01910.Na on a phase I clinical protocol (NCT00533416). RESULTS: ON 01910.Na inhibited cyclin D1 expression, and was selectively toxic to trisomy 8 cells in vitro. Flow cytometry studies demonstrated increased mature CD15+ myeloid cells and decreased CD34+ blasts. Three patients treated with ON 01910.Na on a clinical had decreased bone marrow blasts by ≥ 50%, and three patients had hematologic improvements, one of which was sustained for 33 months. Patients with hematologic responses to ON 01910.Na had decreased cyclin D1 expression in their CD34+ cells. CONCLUSIONS: The preclinical results and responses of patients on a clinical trial warrant further investigation of ON 01910.Na as a potential novel targeted therapy for higher risk MDS patients. |
| | |
Authors:
|
Matthew J Olnes; Aarthie Shenoy; Barbara Weinstein; Loretta Pfannes; Kelsey Loeliger; Zachary Tucker; Xin Tian; Minjung Kwak; Francois Wilhelm; Agnes S M Yong; Irina Maric; Manoj Maniar; Phillip Scheinberg; Jerome Groopman; Neal S Young; Elaine M Sloand |
Related Documents
:
|
11422844 - Study on withdrawal of hypnotics: questionnaire on hypnotic use and its withdrawal. 21729254 - Enhancing patient adherence: outcomes of medication alliance training on therapeutic al... 3946714 - Screening for coinfection with cryptosporidium and giardia in oregon public health clin... 22244674 - Managing side effects of tyrosine kinase inhibitor therapy to optimize adherence in pat... 22233654 - Efficacy and safety of once-daily ritonavir-boosted darunavir plus abacavir/lamivudine ... 12005014 - Rhabdomyolysis of infectious and noninfectious causes. |
Publication Detail:
|
Type: Clinical Trial, Phase I; Journal Article; Research Support, N.I.H., Intramural Date: 2012-04-21 |
Journal Detail:
|
Title: Leukemia research Volume: 36 ISSN: 1873-5835 ISO Abbreviation: Leuk. Res. Publication Date: 2012 Aug |
Date Detail:
|
Created Date: 2012-06-22 Completed Date: 2012-09-05 Revised Date: 2013-04-16 |
Medline Journal Info:
|
Nlm Unique ID: 7706787 Medline TA: Leuk Res Country: England |
Other Details:
|
Languages: eng Pagination: 982-9 Citation Subset: IM |
Copyright Information:
|
Published by Elsevier Ltd. |
Affiliation:
|
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. olnesmj@nhlbi.nih.gov |
| Data Bank Information | |
Bank Name/Acc. No.:
|
ClinicalTrials.gov/NCT00533416 |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Aged Aged, 80 and over Algorithms Antineoplastic Agents / administration & dosage, adverse effects, pharmacology, therapeutic use Bone Marrow Cells / drug effects, pathology Chromosomes, Human, Pair 8 Cyclin D1 / antagonists & inhibitors* Dose-Response Relationship, Drug Female Glycine / administration & dosage, adverse effects, analogs & derivatives*, pharmacology, therapeutic use Humans Male Middle Aged Molecular Targeted Therapy / adverse effects, methods* Myelodysplastic Syndromes / drug therapy*, genetics, pathology Sulfones / administration & dosage, adverse effects, pharmacology, therapeutic use* Trisomy / pathology Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
|
0/Antineoplastic Agents; 0/ON 01910; 0/Sulfones; 136601-57-5/Cyclin D1; 56-40-6/Glycine |
| Comments/Corrections | |
Comment In:
|
Leuk Res. 2012 Aug;36(8):964-5
[PMID:
22607960
]
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Characteristics of stroke mechanisms in patients with medullary infarction.
Next Document: The effect of a controlled 8-week metabolic ward based lysine supplementation on muscle function, in...