Search Results

Understanding Mutations to Treat MDS

Benjamin Ebert is researching what genetic mutations cause myelodysplastic syndromes (MDS), a group of disorders in which the bone marrow fails to produce sufficient blood cells, and how that information can be used to determine prognosis and therapy. MDS frequently progresses to an acute leukemia.

MDS Subtypes

There are several kinds (subtypes) of MDS. The subtype is determined from the results of the blood and bone marrow tests.

WHO Classification

The current WHO classification guidelines identify six subtypes.The current WHO classification guidelines, which were updated in 2022, groups MDS based on genetic abnormalities and morphologically defined features (the appearance and number of the cells under a microscope).

The subtypes are determined by the following:

Development of therapeutic strategy for the treatment of MDS

TP53 mutations are present in 10% of MDS cases and are associated with reduced survival and poor prognosis. However, the effect(s) of TP53 mutations on MDS pathogenesis is unknown. We discovered that MDS cells with TP53 mutations display significant alterations in pre-mRNA splicing due to increased EZH2 activity. We will investigate the mechanisms by which TP53 mutations drive MDS pathogenesis and determine the impact of inhibition of EZH2 and the spliceosome on MDS cells with TP53 mutations.

GNAS as a new therapeutic target for MDS

Myelodysplastic syndrome (MDS) is a blood disease with poor prognosis and frequent progression to acute myeloid leukemia (AML). There are currently no effective treatments. This proposal is based on a recent discovery by my group and proposes to investigate a protein called G⍺s (alpha subunit of the stimulatory G protein), as a novel therapeutic target for MDS. If successful, this work can lead to novel therapies that can transform the treatment of MDS, AML and possibly other cancers.

Myelodysplastic Syndromes (MDS)

Beyond azacitidine: investigating new therapeutic strategies for the treatment of MDS

This proposal aims to understand the molecular mechanisms underlying response to AZA therapy in MDS, as a basis for developing more effective therapies. A ribonucleotide, AZA’s effects on RNA remain unknown. Here, we will investigate the impact of in vivo AZA therapy on RNA alternative splicing and DNA demethylation in MDS patients. Secondly, we will investigate whether AZA treatment exposes neoepitopes in the dysplastic cells of patients, which could be exploited for cancer immunotherapy in MDS

KT1, a novel NK trispecific antibody for the treatment of AML and MDS

New treatments for AML and MDS are urgently needed. We have developed and performed preliminary testing of a novel, patent-protected, trispecific NK cell engager named KT1 which targets AML blasts and leukemia stem cells (LSCs) expressing CD33 and CD123 for elimination by effector cells that express CD16a/b.

Panelists Discuss the AML Patient Experience

What is AML? What research is underway? And what resources are available to patients?

The Leukemia & Lymphoma Society recently joined up with Patient Power and the MDS Alliance to host an AML Awareness Day and answer those questions.

The April 21 webcast was moderated by Carol Preston, host of Patient Power, an online portal offering cancer information for both patients and professionals. Preston is also a chronic lymphocytic leukemia (CLL) survivor.

Luspatercept-aamt

Luspatercept-aamt is FDA approved for the treatment of:

Treatment Advances for Myelodysplastic Syndromes (MDS)

Treatment Update: Myelodysplastic Syndromes (MDS)

Myelodysplastic Syndrome (MDS) Research Funded by LLS

Current and Emerging Therapies for Myelodysplastic Syndromes (MDS)

Current and Emerging Therapies for Myelodysplastic Syndromes (MDS)

Decitabine and cedazuridine

Inqovi is FDA approved for treatment of adult patients with myelodysplastic syndromes (MDS), including previously treated and untreated, de novo and secondary MDS with the following French American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia [CMML]) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups.

 

Metabolically Optimized, Non-cytotoxic Low Dose Weekly Decitabine/Venetoclax in MDS and AML

Dr. Mendel Goldfinger and collaborators of Einstein have shown in a preliminary trial that weekly low dose decitabine plus one a week venetoclax is highly effective in newly diagnosed patients with MDS or AML. The regimen has reduced toxicity compared to the current dose and schedule of azacitidine plus venetoclax. The proposed new work is attempting to demonstrate in a prospective trial at 3 sites that this data can be replicated and expanded.

Ivosidenib

Ivosidenib is FDA approved for the treatment of patients with a susceptible IDH1 mutation as detected by an FDA-approved test in:

FDA Grants Fast Track Designation for Bexmarilimab in r/r MDS

Decitabine

Decitabine is FDA approved to treat adults with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia.

Targeting metabolic reprogramming in MDS and AML stem/progenitor cells

Myelodysplastic neoplasms are malignant disorders driven by expansion of diseased hematopoietic stem cells and progression to leukemia. Our investigations have identified the important role of the transporter of amino acid glutamine SLC38A1 in sustaining metabolic demands of rapidly growing malignant stem cells. The goal of this project is to genetically target this transporter to understand its role on tumorigenesis and progression; and to develop SLC38A1 inhibitors as novel therapeutic tools.

Magrolimab Receives FDA Breakthrough Therapy Designation for Treatment of MDS

A phase 2 study of Bexmarilimab, an anti-Clever1 monoclonal antibody, in combination with azacitidine in patients with high-risk MDS

In June 2022, LLS made an equity investment in Faron Pharmaceuticals to "Support Clinical Development of the Bexmarilimab Program for Leukemia Indications." Faron is a clinical stage biopharmaceutical company developing novel treatments for medical conditions with significant unmet needs caused by dysfunction of our immune system. The Company currently has a pipeline based on the receptors involved in regulation of immune response in oncology, organ damage and bone marrow regeneration. 

Imetelstat

Imetelstat is FDA approved for the treatment of adult patients with low- to intermediate-1 risk myelodysplastic syndromes (MDS) with transfusion-dependent anemia requiring 4 or more red blood cell units over 8 weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESA).