AI Article Synopsis
- Chromosomal abnormalities are common in acute lymphoblastic leukaemia (ALL) but are not enough alone to cause the disease; additional mutations are needed.
- A study analyzed leukaemic cells from 242 children with ALL and found various genetic alterations, particularly in genes that regulate B lymphocyte development, affecting 40% of B-progenitor ALL cases.
- Notably, the PAX5 gene was frequently mutated, leading to decreased protein levels, and other genes like TCF3, EBF1, and IKZF1 also showed deletions, indicating that disruptions in B-cell development pathways are significant contributors to the disease.
Article Abstract
Chromosomal aberrations are a hallmark of acute lymphoblastic leukaemia (ALL) but alone fail to induce leukaemia. To identify cooperating oncogenic lesions, we performed a genome-wide analysis of leukaemic cells from 242 paediatric ALL patients using high-resolution, single-nucleotide polymorphism arrays and genomic DNA sequencing. Our analyses revealed deletion, amplification, point mutation and structural rearrangement in genes encoding principal regulators of B lymphocyte development and differentiation in 40% of B-progenitor ALL cases. The PAX5 gene was the most frequent target of somatic mutation, being altered in 31.7% of cases. The identified PAX5 mutations resulted in reduced levels of PAX5 protein or the generation of hypomorphic alleles. Deletions were also detected in TCF3 (also known as E2A), EBF1, LEF1, IKZF1 (IKAROS) and IKZF3 (AIOLOS). These findings suggest that direct disruption of pathways controlling B-cell development and differentiation contributes to B-progenitor ALL pathogenesis. Moreover, these data demonstrate the power of high-resolution, genome-wide approaches to identify new molecular lesions in cancer.
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| http://dx.doi.org/10.1038/nature05690 | DOI Listing |
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