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Related Concept Videos

Pleiotropy01:33

Pleiotropy

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Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
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Inheritance of Chromatin Structures03:17

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Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
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Multipotency of Hematopoietic Stem Cells01:19

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The hematopoietic stem cells or HSCs are multipotent, meaning they can differentiate and give rise to all blood and immune cells. HSCs are maintained in the quiescent stage until an external stimulus initiates their differentiation. The multipotent HSCs exist as two heterogeneous populations, long-term repopulating cells (LTRC) and short-term repopulating cells (STRC). The two HSC populations have different surface markers or receptors and are classified based on quiescence and long-term...
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Regulation of Hematopoietic Stem Cells01:01

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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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Lineage Commitment01:21

Lineage Commitment

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Commitment is the  process whereby stem cells:
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Hematopoiesis01:21

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The process of blood cell formation is called hematopoiesis. Hematopoiesis starts early during development, on the seventh day of embryogenesis. This phase of hematopoiesis is called the primitive wave, wherein the extraembryonic yolk sac allows the production of erythroid cells and endothelial cells from a common precursor called hemangioblast. The erythroid cells provide oxygen to support the growth of the rapidly dividing embryo. Hemangioblasts later develop into hematopoietic stem cells or...
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Related Experiment Video

Updated: Dec 30, 2025

Flow Cytometry to Estimate Leukemia Stem Cells in Primary Acute Myeloid Leukemia and in Patient-derived-xenografts, at Diagnosis and Follow Up
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ASXL1 mutation in clonal hematopoiesis.

Takeshi Fujino1, Toshio Kitamura1

  • 1Division of Cellular Therapy, The Institute of Medical Science, University of Tokyo, Tokyo, Japan.

Experimental Hematology
|January 17, 2020
PubMed
Summary

Clonal hematopoiesis (CH) involves mutations like ASXL1, increasing cancer risk. Understanding ASXL1

Area of Science:

  • Hematology
  • Molecular Biology
  • Genetics

Background:

  • Clonal hematopoiesis (CH) with somatic mutations affects over 10% of individuals over 65.
  • CH is a pre-malignant condition linked to an increased risk of hematologic malignancies.
  • Somatic mutations in ASXL1 are frequently found in CH and myeloid malignancies.

Purpose of the Study:

  • To review the current literature on ASXL1 mutations in clonal hematopoiesis and myeloid malignancies.
  • To elucidate the role of ASXL1 mutations in the pathogenesis of CH and multi-step tumorigenesis.
  • To discuss the potential causes of CH harboring ASXL1 mutations.

Main Methods:

  • Literature review of studies on ASXL1 mutational landscape and function.
  • Analysis of the involvement of ASXL1 mutations in the pathogenesis of CH and myeloid malignancies.

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  • Discussion of recent findings on ASXL1's role in histone modifications and gene expression.

    • Main Results:

    • ASXL1 mutations, often truncating, are linked to altered histone modifications (H3K4me3, H3K27me3, H2AK119Ub).
    • ASXL1 mutations in mice lead to myeloid transformation but also impaired hematopoietic stem cell (HSC) function.
    • The exact mechanism by which ASXL1 mutations confer a clonal advantage in hematopoietic cells remains unclear.

    Conclusions:

    • ASXL1 mutations play a significant role in the development of CH and myeloid malignancies.
    • Understanding ASXL1's function as a scaffolding protein involved in epigenetic regulation is crucial.
    • Further research is needed to fully elucidate how ASXL1 mutations contribute to CH pathogenesis and clonal advantage.