New research reveals the surprising role of the so-called “jump” gene, which is responsible for the gene mutations that cause many human diseases. In a new study at the Institute for Pediatric Medical Centers in UT Southwestern (CRI), scientists have made an unexpected discovery that these DNA sequences, also known as transposons, can protect against certain blood cancers.
The results of these surveys are Nature geneticsScientists have begun to identify new biomarkers that may help predict how patients will react cancer Find treatments and new therapeutic targets Acute myeloid leukemia (AML), the most deadly type of blood cancer in adults and children.
A transposon is a DNA sequence that, when activated, can move or jump from one place in the genome to another. Although there are many different classes of transposons, scientists at the Xu Institute have focused on a type known as the long-chain interspersed element 1 (L1) retrotransposon. The L1 sequence works by copying and pasting it to various places in the genome. This often results in mutations that can cause diseases such as cancer. Almost half of all cancers contain mutations caused by L1 insertion into other genes, especially lung, colorectal, and head and neck cancers.Incidence of L1 mutations in Blood cancer AML etc. are very low, but the reason is not well understood.
When researchers screened human AML cells to identify genes essential for cancer cell survival, they found that MPP8, a known regulator of L1, was selectively required by AML cells. did. Interested in understanding the underlying basis of this relationship, scientists in the Xu lab studied how the L1 sequence is regulated in human and mouse leukemia cells. They made two important discoveries. First, MPP8 blocked copying the intracellular L1 sequence that initiates AML. Second, when L1 activity was turned on, it could impair the growth or survival of AML cells.
“Our first discovery was surprising because it was long thought that activated transposons promote the development of cancer by generating gene mutations. The opposite is true for hematological cancers, and the reduction in L1 activity is It was found to be associated with patient clinical outcomes and worsening resistance to treatment, said Dr. Jian Xu, CRI Associate Professor and Senior Author of the Study.
Therefore, MPP8 suppressed L1 in order to protect the cancer cell genome and allow AML-initiated cells to survive and proliferate. Cancer cells, like healthy cells, need to maintain a stable genome in order to replicate.Too many mutation, Like those created by L1 activity, can impair the replication of cancer cells. Researchers have found that activation of L1 leads to genomic instability, which activates the DNA damage response, causing cell death and eliminating the ability of cells to replicate themselves. did. Xu believes that this finding may provide an explanation for the mechanism of abnormal susceptibility of myeloid leukemia cells to the DNA damage-inducing therapies currently used to treat patients.
“Our finding that activation of L1 can suppress the survival of certain blood cancers uses L1 as a prognostic biomarker and uses its activity to target cancer cells without normal effects. Open up the possibility of cell“Xu says.
Zhimin Gu et al, LINE-1 Retrotransposon silencing is a selective dependence of myelogenous leukemia, Nature genetics (2021). DOI: 10.1038 / s41588-021-00829-8
UT Southwestern Medical Center
Quote: Scientists, Blood Cancer Obtained from https://medicalxpress.com/news/2021-04-scientists-genes-blood-cancers.html on April 8, 2021 (April 8, 2021) Discovered a “jump” gene that can protect against
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