p190 BCR-ABL mRNA is expressed at low levels in p210-positive chronic myeloid and acute lymphoblastic leukemias

Area of Science:

• Hematology
• Molecular Biology
• Oncology

Background:

• The BCR-ABL fusion gene is a hallmark of certain leukemias, primarily associated with the p210 transcript in chronic myeloid leukemia (CML) and p190 in acute lymphoblastic leukemia (ALL).
• Coexpression of different BCR-ABL transcript variants can occur, potentially influencing disease characteristics and treatment responses.

Purpose of the Study:

• To investigate the prevalence and levels of p190 BCR-ABL mRNA in patients with p210 BCR-ABL-positive leukemias.
• To determine the relationship between p190 and p210 BCR-ABL transcript levels and their potential pathogenetic significance.

Main Methods:

• Analysis of 143 patients with p210 BCR-ABL-positive leukemia, including CML in chronic phase and blast crisis, and p210-positive ALL.
• Detection and quantification of p190 and p210 BCR-ABL mRNA using competitive polymerase chain reaction (PCR).
• Comparison of transcript levels between different disease phases and patient groups, as well as with healthy controls.

Main Results:

• p190 BCR-ABL mRNA was detected in a high percentage of patients: 88% of de novo CML, 100% of CML in blast crisis, 70% of interferon-alpha treated CML, and 100% of p210-positive ALL.
• Transcript numbers for p190 were consistently low compared to p210 BCR-ABL transcripts.
• A significant correlation was observed between p190 and p210 transcript numbers (r = .65, P < .001).
• Median p210 transcript levels were significantly higher in samples positive for p190 compared to those negative for p190.

Conclusions:

• p190 BCR-ABL transcripts are commonly present at low levels in p210 BCR-ABL-positive leukemias.
• The presence of p190 mRNA likely results from alternative splicing or missplicing events.
• The low-level coexpression of p190 BCR-ABL mRNA is probably not of pathogenetic significance in these leukemias.