scholarly journals Hypomethylating agents in combination with histone deacetylase inhibitors in higher risk myelodysplastic syndromes: Is there a light at the end of the tunnel?

Cancer ◽  
2017 ◽  
Vol 123 (6) ◽  
pp. 911-914 ◽  
Author(s):  
Maximilian Stahl ◽  
Amer M. Zeidan
Keyword(s):  
Histone Deacetylase ◽  
Myelodysplastic Syndromes ◽  
Histone Deacetylase Inhibitors ◽  
Hypomethylating Agents

Six (or More) Drugs in Search of a Mechanism: DNA Methyltransferase and Histone Deacetylase Inhibitors in the Treatment of Myelodysplastic Syndromes

2006 ◽  
Vol 4 (1) ◽  
pp. 83-90 ◽  
Author(s):  
Steven D. Gore
Keyword(s):  
Histone Deacetylase ◽  
Myelodysplastic Syndromes ◽  
Dna Methyltransferase ◽  
Histone Deacetylase Inhibitors ◽  
Conclusive Evidence ◽  
Clinical Activity ◽  
Dna Methyltransferase Inhibitors ◽  
Expression Of Genes ◽  
Measurable Activity ◽  
Epigenetic Modulation

The clinical activity of the DNA methyltransferase inhibitors 5-azacitidine and 2′-deoxy-5-azacytidine in myelodysplastic syndromes (MDS) suggests that epigenetic modulation of gene transcription may play an important pathogenetic role in the development and expression of these diseases. Approximately 50% of patients treated with these compounds experience hematologic improvement, making these the most active single agents for unselected patients with MDS. Responses include complete and partial hematologic responses. Two randomized trials have shown that the use of these drugs significantly alters the natural history of MDS compared with supportive care. Histone deacetylase inhibitors, which may also impact the expression of genes through epigenetic mechanisms, seem to have measurable activity in MDS in preliminary studies. Histone deacetylase inhibitors are most likely used in combination with other agents, including DNA methyltransferase inhibitors. Despite the clinical activity of these classes of drugs, there is no conclusive evidence that their clinical activity is attributable to their impact on the epigenome. Such information will be critical in the development of more effective congeners and drug combinations in ongoing attempts to improve the outcome of patients with MDS.

Decitabine Induces High Response Rates in Patients with Chronic Myelomonocytic Leukemia (CMML).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2655-2655
Author(s):  
Elias Jabbour ◽  
Susan O’Brien ◽  
Farhad Ravandi-Kashani ◽  
Jorge Cortes ◽  
Gautam Borthakur ◽  
...  
Keyword(s):  
Growth Factors ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Chromosomal Abnormalities ◽  
Chronic Myelomonocytic Leukemia ◽  
Study Group ◽  
Hypomethylating Agents ◽  
Future Studies ◽  
Prior Therapy ◽  
Myelomonocytic Leukemia

Abstract Background The hypomethylating agents decitabine and azacitidine have significant anti-myelodysplastic (MDS)activity and have been FDA approved for the treatment of MDS and CMML. Experience in CMML has been minimal. Study Aims Evaluate the efficacy of decitabine in CMML. Study Group and Treatment Patients with CMML received decitabine 20 mg/m2 IV/1 hour daily x 5 or 2 alternative schedules, delivering 100 mg/m2/course every four weeks (Kantarjian, Blood 2006). Response was evaluated by the modified IWG criteria (Cheson, Blood 2006). Results Nineteen patients were treated. Their median age was 66 years (range 44–82 years). Splenomegaly was present in 4 (21%); hemoglobin less than 10 g/dL in 10 (53%); thrombocytopenia less than 100 x 109/L in 12 (63%); WBC more than 40 x 109/L in 5 (26%); chromosomal abnormalities in 6 (32%); prior therapy for CMML in 9 (47%); marrow or peripheral blast 5% or more in 11 (58%). Overall, 13 patients (69%) achieved IWG responses: CR in 11 (58%), other HI in 2 (11%). Improvement of thrombocytopenia was noted in 7/8 patients (88%) with pretreatment platelets less than 50 x 109/L. Median survival was 19 months. Among 6 patients with pretreatment chromosomal abnormalities who achieved response, 1 (17%) had disappearance, and 2 had > 50% reduction of cytogenetic abnormalities. Extramedullary toxicities were minimal. Conclusions Decitabine is active and safe in CMML. Future studies may combine decitabine with histone deacetylase inhibitors, chemotherapy (eg cytarabine, topotecan), or growth factors.

scholarly journals The combination of hypomethylating agents and histone deacetylase inhibitors produce marked synergy in preclinical models of T-cell lymphoma

2015 ◽  
Vol 171 (2) ◽  
pp. 215-226 ◽  
Author(s):  
Enrica Marchi ◽  
Kelly M. Zullo ◽  
Jennifer E. Amengual ◽  
Matko Kalac ◽  
Danielle Bongero ◽  
...  
Keyword(s):  
T Cell ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Hypomethylating Agents ◽  
Preclinical Models
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