A new study found that heme biosynthesis promotes the progression of acute myeloid leukemia (AML), an aggressive type of blood cancer.
Scientists have proposed to suppress heme production for the treatment of leukemia along with other existing therapies.
Only in 2014 in the United States leukemia struck 387 thousand people, according to statistics of the National Cancer Institute.
Among all types of blood cancer, acute myeloid leukemia is considered one of the most dangerous and difficult to treat. For this year, US doctors have counted 21,380 new cases of AML, with 10,590 patients died, despite the impressive capabilities of local medicine.
The St. Jude Children's Research Hospital in Memphis annually receives about 500 small patients with AML for treatment, the second most common cancer in children.
A study by Dr. John Shuets from St Jude's Children's Research Hospital shed light on the pathogenesis of a fatal disease, which in the future will significantly improve survival in AML. Independent experts interviewed by the MNT publication call this discovery a breakthrough in oncohematology.
Biosynthesis of heme stimulates leukemia.
The hem is a porphyrin compound that is used to synthesize hemoglobin, the main oxygen carrier in human blood. In the process of cellular respiration, gem is responsible for electron transfer.
Only recently it was found that gem helps leukemia cells survive in unfavorable conditions. On the pages of JCI Insight, the team of Dr. Shuets argues that by blocking the heme products, it is possible to make malignant cells vulnerable to traditional chemotherapy and destroy.
Dr. Schuetz stresses the importance of this discovery, as previously it was not possible to trace the even relationship between heme production and leukemia cells. This is a completely new direction.
The first step in the unique study was to view the database of St Jude's, which stores detailed results of blood tests of sick children. The researchers found a regularity: with particularly aggressive myeloid leukemia, the MYCN oncogene is activated, which plays a key role in the division and self-destruction of cells.
The second, the most important discovery was the activation of the gene UROD (uroporphyrinogen decarboxylase) - a stimulator of heme products. In children with an aggressive form of acute myeloid leukemia (AML), this gene was excessively active, which clearly indicates a relationship between heme production and the progression of acute myeloblastic leukemia.
According to Shuets, myeloid leukemia, which is accompanied by activation of the MYCN oncogene and increased expression of the UROD gene, is extremely difficult and often results in death of patients.
It has been experimentally proved that stopping the biosynthesis of heme by gene therapy leads to a slowdown in the progression of leukemia and increases the effectiveness of chemotherapy drugs.
New possibilities for the therapy of acute myeloid leukemia (AML).
Blocking the heme production was easier than it seems - just remove the MYCN gene and the key component of its biosynthesis. This leads to the accumulation of molecules that are toxic to leukemia cells. Preclinical animal experiments confirmed the advisability of such an approach: the progression of leukemia slowed, the survival rate increased significantly.
"In animal models, two approaches to AML therapy are tested. The first is the selective blocking of the UROD gene. The second strategy is taking drugs that suppress MYCN, along with the use of the heme precursor. The very molecule that is dangerous for cancer cells, "explains Dr. Shuets.
The results of a unique study can be applied in other areas of oncology. For example, for the treatment of medulloblastoma and other tumors, accompanied by excessive production of heme.
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