Modification of hematopoietic stem cell fate by 5aza 2'deoxycytidine and trichostatin A.
5azaD and TSA can be used to alter the fate of primitive HSCs/HPCs during in vitro culture and retain the ability to repopulate immunodeficient mice, demonstrating that DNA methylation and histone deacetylation are components of an epigenetic program that regulates gene expression.
Maintenance of elevated fetal hemoglobin levels by decitabine during dose interval treatment of sickle cell anemia.
The absence of cumulative toxicity may allow shorter intervals between drug treatments, which may lead to higher hemoglobin and HbF levels after several treatment cycles and, therefore, to greater clinical improvement.
Effects of 5-aza-2'-deoxycytidine on fetal hemoglobin levels, red cell adhesion, and hematopoietic differentiation in patients with sickle cell disease.
Subcutaneous subcutaneous decitabine produces cumulative increases in HbF and total hemoglobin through a noncytotoxic mechanism of action and chronic dosing and sustained increases in hemoglobin F andtotal hemoglobin levels may be possible.
2-deoxy 5-azacytidine and fetal hemoglobin induction in sickle cell anemia.
5-aza-CdR could be effective in increasing HbF in patients with sickle cell anemia who failed to increase HfF with Hydroxyurea, and demonstration of sustained F levels with additional treatment cycles without toxicity is currently being performed.
Hydroxymethylation at gene regulatory regions directs stem/early progenitor cell commitment during erythropoiesis.
Oral tetrahydrouridine and decitabine for non-cytotoxic epigenetic gene regulation in sickle cell disease: A randomized phase 1 study
Administration of oral THU-decitabine to patients with SCD was safe in this study and, by targeting DNMT1, upregulated HbF in RBCs, indicating better RBC quality, biomarkers of hemolysis, thrombophilia, and inflammation improved.
Inhibition of myeloma cell growth by dexamethasone and all-trans retinoic acid: synergy through modulation of interleukin-6 autocrine loop at multiple sites.
The study demonstrates the possibility of regulating myeloma cell growth through modulation of IL-6/IL-6R autocrine/paracrine loop and the principle of achieving a synergistic effect by blocking this loop at multiple sites.
Pharmacological inhibition of LSD1 and mTOR reduces mitochondrial retention and associated ROS levels in the red blood cells of sickle cell disease.
Histone deacetylase inhibitors increase p21WAF1 and induce apoptosis of human myeloma cell lines independent of decreased IL‐6 receptor expression
- D. Lavelle, Y. H. Chen, M. Hankewych, J. Desimone
- BiologyAmerican journal of hematology/oncology
- 1 November 2001
Results indicated that decreased IL‐6R expression was not required for induction of p21WAF1 or apoptosis, and their use in the treatment of myeloma, particularly in combination with other agents, warrants further investigation.
The LSD1 inhibitor RN-1 induces fetal hemoglobin synthesis and reduces disease pathology in sickle cell mice.
It is indicated that RN-1 can effectively induce HbF levels in red blood cells and reduce disease pathology in SCD mice, and may therefore offer new therapeutic possibilities for treating SCD.