Health
Researchers identify potential new classes of drugs to treat blood and bone marrow cancers
A group of US scientists, including Indian-Americans at the renowned Cleveland Clinic, are new that may prove effective in treating certain common types of blood group and bone marrow type cancers. Identified the drug in the class.
First published in the latest version of Blood cancer Discovery, a decade-long study reporting new pharmacological strategies for preferentially targeting and eliminating leukemia cells with TET2 mutations, collaborated with Jaroslaw Maciejewski of the Cleveland Clinic’s Translation Hematology and Oncology Research Division. Performed by Babal Kant Jha.
Myeloid leukemia is a cancer derived from bone marrow stem and progenitor cells that gives rise to all normal blood cells. One of the most common mutations involved in the development of myeloid leukemia is found in the TET2 gene, which has been investigated by Maciejewski and Jha for the past decade.
“In the preclinical model, a synthetic molecule called TETi76 targets and kills mutant cancer cells both in the early stages of the disease (so-called uncertain clonal hematopoiesis, or CHIP) and in fully developed TET2 mutant bone marrow. It turns out that we can do it. Leukemia, “said Dr. Maciejewski.
According to the media release, the research team designed TETi76 to replicate and amplify the effect of a natural molecule called 2HG (2-hydroxyglutarate) that inhibits the enzymatic activity of the TET gene.
The TET DNA dioxygenase gene family encodes an enzyme that removes chemical groups from DNA molecules. This can alter the genes that are ultimately expressed, which can contribute to the onset and spread of the disease.
Although all members of the TET family are dioxygenases, the press release states that the most potent enzymatic activity belongs to TET2. However, even if TET2 is mutated, its associated genes, TET1 and TET3, provide residual enzyme activity.
Significantly less, this activity is sufficient to promote the spread of mutated cancer cells.
Maciejewski and Jha’s new pharmacological strategy for the selective elimination of TET2-mutant leukemic cells is focused on targeting this dependence on residual DNA dioxygenase activity, he said.
“We learned lessons from 2HG’s natural biological capabilities,” explained lead researcher Jha.
“We studied the molecule and reasonably designed a new small molecule synthesized by a chemical group led by Dr. James Phillips. Together, not only TET2, but also the enzymatic activity that causes the rest of TET1 and TET3. We have produced a similar but more powerful version of TETi76 that can be inhibited, “said Jha.
The Cleveland Clinic said researchers have studied the effects of TETi76 in both preclinical disease and xenograft models, where human cancer cells are transplanted into the preclinical model. Additional research will be important to investigate the ability of patients to fight small molecule cancers.
“We are optimistic about the results showing that TETi76 not only preferentially limits the growth and spread of cells with the TET2 mutation, but also provides survival benefits to normal stem and progenitor cells,” Jha said. I am.
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