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RT-PCR Analysis of Breakpoints Involving the MLL Gene Located at 11q23 in Acute Leukemia
1LRF Department of Haematology and Oncology, Institute of Child Health, University of London, UK.
Methods in Molecular Medicine
|March 8, 2011
Summary
Chromosome 11 rearrangements involving band 11q23 are common in infant and adult leukemias. The MLL gene, a potential regulator of gene expression, is implicated in these leukemias, which often show poor chemotherapy response.
Area of Science:
- Genetics
- Oncology
- Molecular Biology
Background:
- Chromosome 11 rearrangements at band 11q23 are frequently observed in various types of leukemia, including infant, childhood, and adult acute leukemias of both myeloid and lymphoid origins.
- These specific leukemias (7-10% of acute lymphoblastic leukemia, 5-6% of acute nonlymphocytic leukemia) are often characterized by CD10 expression, a biphenotypic or mixed-lineage phenotype, and a poor prognosis with standard chemotherapy.
- The gene located at 11q23, known as MLL (also referred to as ALL-1, HRX, or HTRX), has been identified as the key player in these chromosomal rearrangements.
Purpose of the Study:
- To characterize the MLL gene involved in 11q23 rearrangements in acute leukemias.
- To understand the molecular and cytogenetic basis of these specific leukemia subtypes.
- To investigate the potential role of the MLL gene in gene expression regulation.
Main Methods:
- Cytogenetic analysis to detect chromosome 11 rearrangements at band 11q23.
- Molecular cloning and characterization of the involved gene.
- Bioinformatic analysis to identify functional domains and homology to known regulatory genes.
Main Results:
- High proportion of infant, childhood, and adult acute leukemias exhibit 11q23 rearrangements.
- The MLL gene, encoding a large polypeptide, was identified at the 11q23 locus.
- MLL exhibits homology to Drosophila trithorax, suggesting a role in gene expression regulation.
- MLL possesses DNA-binding domains characteristic of a transcription factor.
Conclusions:
- Chromosome 11 rearrangements at 11q23 are significant events in a substantial percentage of acute leukemias.
- The MLL gene is critically involved in these rearrangements and likely plays a role in leukemogenesis.
- The structural characteristics of MLL suggest its function as a transcription factor, potentially disrupting normal gene expression patterns in leukemia.
