A Nested Reverse Transcription-Polymerase Chain Reaction Assay to Detect BCR/abl

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• Chronic myelogenous leukemia (CML) and certain acute lymphoblastic leukemias (ALLs) are linked to the Philadelphia chromosome, a specific chromosomal abnormality.
• This abnormality, denoted as t(9;22)(q34;q11), involves a translocation between chromosomes 9 and 22.
• The translocation fuses the BCR gene from chromosome 22 with the ABL proto-oncogene from chromosome 9.

Purpose of the Study:

• To elucidate the genetic basis of Philadelphia chromosome-positive leukemias.
• To understand the role of the BCR/ABL fusion protein in leukemogenesis.

Main Methods:

• Cytogenetic analysis to identify the t(9;22)(q34;q11) translocation.
• Molecular techniques to characterize the BCR/ABL fusion gene and protein.
• Functional studies to assess the tyrosine kinase activity of the BCR/ABL protein.

Main Results:

• The Philadelphia chromosome results from the joining of the M-bcr region of chromosome 22 with the c-abl proto-oncogene on chromosome 9.
• This chromosomal translocation generates a BCR/ABL fusion gene.
• The resulting BCR/ABL fusion protein exhibits enhanced tyrosine kinase activity.

Conclusions:

• The BCR/ABL fusion protein's increased tyrosine kinase activity is crucial for the pathogenesis of CML and Philadelphia chromosome-positive ALL.
• Understanding this molecular mechanism is vital for developing targeted therapies for these leukemias.