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Generation of a MLL-AF9-specific stem cell model of acute monocytic leukemia

Men Yee Chiew1, Nem Yun Boo1, Kenny Voon2

  • 1a Faculty of Medicine and Health Sciences , Universiti Tunku Abdul Rahman , Kajang , Malaysia.

Leukemia & Lymphoma
|May 18, 2016
PubMed

Insights

Researchers created induced pluripotent stem cells (iPSCs) from acute monocytic leukemia (AML-M5) cells. These AML-M5 iPSCs offer a new model for studying this aggressive childhood cancer.

Area of Science:

  • Hematology
  • Stem Cell Biology
  • Pediatric Oncology

Background:

  • Acute monocytic leukemia (AML-M5) predominantly affects children and is associated with a poor prognosis.
  • The underlying mechanisms contributing to treatment failure in AML-M5 remain largely unknown.
  • Understanding AML-M5 pathogenesis is crucial for developing effective therapeutic strategies.

Purpose of the Study:

  • To generate induced pluripotent stem cells (iPSCs) from a patient with AML-M5.
  • To characterize these AML-M5-derived iPSCs for their pluripotency and disease-specific markers.
  • To establish a novel cellular model for investigating AML-M5.

Main Methods:

  • Generation of iPSCs from THP-1 cells (AML-M5 patient) using retroviral transduction of OCT3/4, SOX2, KLF4, and c-MYC.
  • Assessment of iPSC characteristics including morphology, gene expression, protein/antigen expression, and differentiation potential.
  • Detection of the MLL-AF9 fusion gene in iPSC clones and parental cells.

Main Results:

  • Successfully generated AML-M5-derived iPSC clones exhibiting characteristics similar to human embryonic stem cells.
  • Demonstrated down-regulation of parental-specific markers in the generated iPSCs.
  • Confirmed the presence of the MLL-AF9 fusion gene, associated with AML-M5 pathogenesis, in all iPSC clones.

Conclusions:

  • AML-M5-specific iPSC clones were successfully developed, representing a significant advancement.
  • These iPSCs provide a valuable disease model for future research into AML-M5.
  • This model holds potential for advancing the study of AML-M5 pathogenesis and therapeutic interventions.
Keywords:
Acute monocytic leukemiaMLL-AF9acute myeloid leukemiainduced pluripotent stem cells

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