A specific linkage between the incidence of TP53 mutations and type of chromosomal translocations in B-precursor acute lymphoblastic leukemia cell lines.

Chromosomal translocation plays an essential role in leukemogenesis of childhood B-precursor acute lymphoblastic leukemia (ALL) in combination with specific gene mutations. Although several reports suggest correlation of TP53 mutation with the type of chromosomal translocation in childhood B-precursor ALL, it has not been directly confirmed in a single cohort study due to the limited incidence of TP53 mutation in primary samples at diagnosis. Leukemia cell lines generally show higher incidence of gene mutations compared with primary samples. Thus, to clarify possible differences in cooperation of the p53 pathway for leukemogenesis with the type of chromosomal translocation, TP53 gene mutation was analyzed in 32 B-precursor ALL cell lines. TP53 mutation was observed in 40.6% (13 cell lines), and missense mutation of R248Q was the most commonly observed (5 cell lines). Of note, TP53 mutation was frequently observed among MLL-rearranged and t(1;19)-positive ALL cell lines, but was very rare among Philadelphia chromosome-positive and t(17;19)-positive ALL cell lines. Although the number of samples analyzed is limited, this is the first direct observation of the correlation between the incidence of TP53 mutation and types of translocation in B-precursor ALLs, suggesting a functionally different fusion gene product in the p53 pathway for leukemogenesis.