Transcriptional Silencing of MCL-1 Through Cyclin-Dependent Kinase Inhibition in Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is the most common adult acute leukemia. Survival remains poor, despite decades of scientific advances. Cytotoxic induction chemotherapy regimens are standard-of-care for most patients. Many investigations have highlighted the genomic heterogeneity of AML, and several new targeted therapeutic options have recently been approved. Additional novel therapies are showing promising clinical results and may rapidly transform the therapeutic landscape of AML. Despite the emerging clinical success of B-cell lymphoma (BCL)-2 targeting in AML and a large body of preclinical data supporting myeloid leukemia cell (MCL)-1 as an attractive therapeutic target for AML, MCL-1 targeting remains relatively unexplored, although novel MCL-1 inhibitors are under clinical investigation. Inhibitors of cyclin-dependent kinases (CDKs) involved in the regulation of transcription, CDK9 in particular, are being investigated in AML as a strategy to target MCL-1 indirectly. In this article, we review the basis for CDK inhibition in oncology with a focus on relevant preclinical mechanism-of-action studies of CDK9 inhibitors in the context of their therapeutic potential specifically in AML.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research

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ConclusionOur study did not find a statistically significant difference in the overall response rates or survival outcome measures for patients with AML and indeterminate day 14 bone marrow in the 2 treatment groups. Our findings question the utility of immediate reinduction chemotherapy and raise concern regarding overtreatment in this patient population. Larger studies investigating similar outcomes are warranted to validate our clinical findings.
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
ConclusionsThe high ORR and reasonable duration of response could allow for potentially curative allogeneic hematopoietic cell transplantation for these patients with high-risk AML. Our initial data suggest that lenalidomide plus HMA is a promising approach for patients with AML with inv(3).
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
ConclusionsThis is the first multicenter report analyzing AML-survival in Mexico. Challenges in this setting include a high induction-related mortality and low AlloHSCT rate, which should be addressed in order to improve outcomes.
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
Publication date: Available online 24 December 2019Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Yedla Rajani Priya, Stalin Chowdary Bala, Venkateswara Rao Pydi, Kuruva Siva Prasad, Rachana Chennamaneni, Meher Lakshmi Konatam, Tara Roshni Paul, Sadashivudu GundetiAbstractBackgroundAcute promyelocytic leukemia, a distinct variant of acute myeloid leukemia (AML) accounts for 10% of AML cases. Over the past decade, APL had emerged from a highly fatal disease to a highly curable one. The published data on outcomes of APL from India is scant. The present study was designed to analyse the clinicopathological features ...
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
Publication date: Available online 24 December 2019Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Prajwal Dhakal, Bimatshu Pyakuryal, Prasun Pudasainee, Venkat Rajasurya, Krishna Gundabolu, Vijaya Raj BhattAbstractProspective evidence for management of therapy-related acute myeloid leukemia (t-AML) is limited, with evidence extrapolated from major AML trials. Optimal treatment is challenging and needs consideration of patient-specific, disease-specific, and therapy-specific factors. Clinical trials are recommended, especially for unfit patients or those with unfavorable cytogenetics or mutations. CPX-351 as an up...
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
CONCLUSIONThe findings highlight a significant burden associated with CDI in haematological patients undergoing induction chemotherapy in the US. There is an important need for prevention of CDI in this specific patient population.
Source: Journal of Hospital Infection - Category: Infectious Diseases Source Type: research
Publication date: Available online 26 November 2019Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Eytan M. Stein, Courtney D. DiNardo, Daniel A. Pollyea, Andre C. SchuhAbstractThe ultimate goal of treatment for acute myeloid leukemia (AML) is to improve survival, and the best means of doing so is through the induction of morphologic remission, which is historically most reliably achieved with intensive chemotherapy regimens. Older patients with AML are less likely to be candidates for or to benefit from intensive chemotherapy. Patients deemed ineligible for intensive therapy may nevertheless benefit from lower-in...
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
Publication date: Available online 26 November 2019Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Eytan M. Stein, Courtney D. DiNardo, Daniel A. Pollyea, Andre C. SchuhAbstractThe ultimate goal of treatment for acute myeloid leukemia (AML) is to improve survival, and the best means of doing so is through the induction of morphologic remission, historically most reliably achieved with intensive chemotherapy regimens. Older patients with AML are less likely to be candidates for, or to benefit from, intensive chemotherapy. Patients deemed ineligible for intensive therapy may nevertheless benefit from lower intensity...
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
The ultimate goal of treatment for acute myeloid leukemia (AML) is to improve survival, and the best means of doing so is through the induction of morphologic remission, which is historically most reliably achieved with intensive chemotherapy regimens. Older patients with AML are less likely to be candidates for or to benefit from intensive chemotherapy. Patients deemed ineligible for intensive therapy may nevertheless benefit from lower-intensity therapies and from newly available targeted AML treatments.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Tags: Review Source Type: research
The ultimate goal of treatment for acute myeloid leukemia (AML) is to improve survival, and the best means of doing so is through the induction of morphologic remission, historically most reliably achieved with intensive chemotherapy regimens. Older patients with AML are less likely to be candidates for, or to benefit from, intensive chemotherapy. Patients deemed ineligible for intensive therapy may nevertheless benefit from lower intensity therapies and from newly available, targeted AML treatments.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Tags: Review Article Source Type: research
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