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Related Concept Videos

Regulation of Hematopoietic Stem Cells01:01

Regulation of Hematopoietic Stem Cells

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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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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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Commitment is the  process whereby stem cells:
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Regulation of Angiogenesis and Blood Supply01:24

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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
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Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust...
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The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
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Related Experiment Video

Updated: Jul 1, 2025

Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells
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Regulation of HOX gene expression in AML.

Irum Khan1,2, Mohammed A Amin1, Elizabeth A Eklund1,2,3

  • 1Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA.

Blood Cancer Journal
|March 7, 2024
PubMed
Summary

HOX gene regulation in acute myeloid leukemia (AML) is complex, particularly in NPM1-mutated AML. Understanding these mechanisms offers new therapeutic strategies for AML patients.

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Area of Science:

  • Hematopoiesis and Cancer Biology
  • Molecular Oncology
  • Gene Regulation in Leukemia

Background:

  • HOX cluster genes are crucial developmental regulators with context-specific roles in normal and malignant hematopoiesis.
  • Leukemia cells exhibit complex HOX gene expression orchestrated by transcription factors, epigenetic regulators, and chromatin changes.
  • This review focuses on HOX regulation in acute myeloid leukemia (AML), especially in NPM1-mutated AML, a common subtype.

Approach:

  • Summarizes molecular mechanisms of HOX regulation in clinical AML subsets.
  • Highlights the paradoxical observation of favorable treatment responses despite HOX gene upregulation in NPM1-mutated AML.
  • Reviews recent findings on FOXM1, mutant NPM, and the menin-MLL interaction in HOX regulation.

Key Points:

  • FOXM1 inactivation may link cytoplasmic NPM to HOX upregulation, while nuclear NPM modifies chromatin to permit HOX expression.
  • Menin-MLL inhibitors show clinical activity in NPM1/MLL-rearranged AML but with inconsistent HOX locus suppression.
  • Targeting HOX regulation presents a potential strategy across major AML subtypes.

Conclusions:

  • Context-specific HOX regulation in AML is key to understanding therapeutic vulnerabilities.
  • Further insights into HOX gene control can inform novel treatment approaches for AML.
  • Targeting common vulnerabilities in HOX-dependent AML may improve patient outcomes.