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MLL fusions: pathways to leukemia.

Han Liu1, Emily H Y Cheng, James J D Hsieh

  • 1Molecular Oncology, Department of Medicine, Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO 63110, USA.

Cancer Biology & Therapy
|September 5, 2009
PubMed
Summary
This summary is machine-generated.

Chromosomal aberrations involving the MLL gene are linked to poor prognosis in human leukemias, particularly infant cases. Understanding MLL

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Area of Science:

  • Molecular Biology
  • Genetics
  • Oncology

Background:

  • Chromosomal band 11q23 aberrations disrupting the MLL gene are associated with poor prognosis in human leukemias.
  • MLL-associated leukemias are prevalent in infants and contribute to adult and therapy-related acute leukemias.

Purpose of the Study:

  • To summarize the biological and pathological roles of MLL and its fusion proteins in leukemogenesis.
  • To discuss current models and potential therapeutic strategies for MLL-associated leukemias.

Main Methods:

  • Review of recent studies on MLL gene function and its role in leukemia.
  • Analysis of MLL gene processing, including Taspase1 activity.
  • Examination of MLL translocation partner genes (TPGs) and their fusion mechanisms.

Main Results:

  • The MLL precursor (500 kD) is processed by Taspase1 into mature MLL(N320/C180), crucial for embryogenesis, cell cycle, and stem cell maintenance.
  • Leukemogenic MLL translocations involve the MLL N-terminus fused to over 60 TPGs.
  • Recent research has significantly advanced understanding of MLL's normal functions and its deregulation in leukemia.

Conclusions:

  • MLL and its fusions play critical roles in both normal biological processes and leukemogenesis.
  • Further research into MLL's functions and deregulation is vital for developing targeted therapies.
  • Available models and potential therapeutic targets for MLL-associated leukemias are discussed.