Related Experiment Video

Updated: Mar 12, 2026

Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells
10:21

Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells

Published on: February 21, 2018

10.6K

Instructive Role of MLL-Fusion Proteins Revealed by a Model of t(4;11) Pro-B Acute Lymphoblastic Leukemia

Shan Lin1, Roger T Luo2, Anetta Ptasinska3

  • 1Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.

Cancer Cell
|November 16, 2016
PubMed

Insights

A new model of mixed-lineage leukemia (MLL)-AF4 pro-B acute lymphoblastic leukemia (ALL) was created. This model fully recapitulates the human disease and aids in understanding leukemogenesis.

Area of Science:

  • Hematology
  • Molecular Biology
  • Oncology

Background:

  • The t(4;11) translocation creates the MLL-AF4 fusion, a common driver in acute lymphoblastic leukemia (ALL).
  • Existing models do not fully capture the complexity of MLL-AF4 driven B-ALL.

Purpose of the Study:

  • To develop a robust preclinical model of MLL-AF4 positive B-ALL.
  • To investigate the distinct molecular mechanisms of MLL-Af4 compared to other MLL fusions.
  • To study the lineage plasticity observed in t(4;11) ALL.

Main Methods:

  • Generation of high-titer retrovirus encoding MLL-Af4.
  • Transduction of human CD34+ hematopoietic stem cells.
  • Immunophenotypic and molecular characterization of the generated leukemia model.
  • Comparative analysis of MLL-Af4 and MLL-AF9 fusion proteins' genomic targets.

Main Results:

  • MLL-Af4 efficiently transduced human CD34+ cells, creating a faithful model of t(4;11) B-ALL.
  • MLL-Af4 induced distinct gene expression patterns compared to MLL-AF9 due to differential target binding.
  • The MLL-Af4 model exhibited lineage plasticity, switching to a myeloid state while retaining lymphoid potential, mirroring patient observations.

Conclusions:

  • The MLL-Af4 retroviral model is a valuable tool for studying t(4;11) B-ALL pathogenesis.
  • Understanding lineage plasticity is crucial for developing effective therapies against MLL-AF4 ALL.
  • This model can facilitate the discovery of novel therapeutic strategies for MLL-AF4 leukemias.
Keywords:
MLL-AF4acquired resistance to targeted therapyacute lymphoblastic leukemiachimeric fusion proteinsmouse models of cancerspecies specificity of oncogenes

More Related Videos

Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing09:49

Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing

Published on: July 5, 2019

10.1K
Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

890

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.4K
Differentiation of Common Myeloid Progenitor Cells01:15

Differentiation of Common Myeloid Progenitor Cells

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...
4.2K