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Related Concept Videos

MicroRNAs01:22

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MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
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All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
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ADARs Edit MicroRNAs to Promote Leukemic Stem Cell Activity.

Wen Cai Zhang1, Frank J Slack1

  • 1Institute for RNA Medicine, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.

Cell Stem Cell
|August 6, 2016
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Summary

Targeting the RNA editing enzyme ADAR1 can restore let-7 expression and kill leukemic stem cells (LSCs) in chronic myeloid leukemia (CML). This finding offers a novel therapeutic strategy for CML treatment.

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Area of Science:

  • Hematology
  • Molecular Biology
  • Cancer Research

Background:

  • Leukemic stem cells (LSCs) are critical drivers of chronic myeloid leukemia (CML) progression.
  • Mechanisms underlying LSC-driven CML and tyrosine kinase inhibitor (TKI) resistance are not fully understood.

Purpose of the Study:

  • To investigate novel therapeutic targets for chronic myeloid leukemia (CML).
  • To explore the role of RNA editing in LSC function and CML pathogenesis.

Main Methods:

  • The study focused on the RNA editing enzyme ADAR1.
  • Investigated the impact of targeting ADAR1 on let-7 microRNA expression.
  • Assessed the effect of ADAR1 targeting on leukemic stem cell (LSC) viability.

Main Results:

  • Targeting ADAR1 was shown to restore the expression of let-7 microRNAs.
  • Efficient killing of leukemic stem cells (LSCs) was observed upon ADAR1 inhibition.
  • This suggests a direct link between ADAR1 activity, let-7 levels, and LSC survival.

Conclusions:

  • The RNA editing enzyme ADAR1 represents an innovative therapeutic target in chronic myeloid leukemia (CML).
  • Restoring let-7 expression by targeting ADAR1 offers a promising strategy for eradicating CML stem cells.