PAX5, a master regulator of B-cell development, was recently shown to be involved in several leukemia-associated rearrangements, which result in fusion genes encoding chimeric proteins that antagonize PAX5 transcriptional activity. In a population-based fluorescence in situ hybridization screening study of 446 childhood acute lymphoblastic leukemia (ALL) patients, we now show that PAX5 rearrangements occur at an incidence of about 2.5% of B-cell precursor ALL. Identification of several novel PAX5 partner genes, including POM121, BRD1, DACH1, HIPK1 and JAK2 brings the number of distinct PAX5 inframe fusions to at least 12. Our data show that these not only comprise transcription factors but also structural proteins and genes involved in signal transduction, which at least in part have not been implicated in tumorigenesis.

The aim of the present study was to determine the frequency and clinical relevance of the most common secondary karyotype abnormalities in TEL/AML1 þ B-cell precursor acute lymphoblastic leukemia (ALL) as assessed with fluorescence in situ hybridization (FISH) analyses. Screening of 372 patients who were enrolled in two consecutive Austrian childhood ALL multicenter trials identified 94 (25%) TEL/AML1 þ cases. TEL deletions, trisomy 21 and an additional der(21)t(12;21) were detected in 52 (55%), 13 (14%) and 14 (15%) TEL/AML1 þ patients, respectively. The 12p aberrations (P ¼ 0.001) and near tetraploidy (P ¼ 0.045) were more common in TEL/AML1 þ patients, whereas the incidence of diploidy, pseudodiploidy, hypodiploidy, low hyperdiploidy, near triploidy, del(6q), chromosome 9 and 11q23 abnormalities was similar among TEL/ AML1 þ and TEL/AML1À patients. None of the TEL/AML1 þ patients had a high hyperdiploid karyotype. Univariate analysis indicated that among TEL/AML1 þ patients those with a deletion of the nontranslocated TEL allele had a worse prognosis than those without this abnormality (P ¼ 0.034). We concluded that the type and incidence of the most common secondary aberrations in TEL/AML1 þ ALL can be conveniently identified with little additional effort during interphase screening with appropriate TEL and AML1 FISH probes. We also provided preliminary evidence that the deletion of the nontranslocated TEL allele may adversely influence the clinical course of TEL/AML1 þ ALL.

The overall and early relapse rates in the BFM study were lower than that in a previous United Kingdom Medical Research Council/Childhood Leukemia Working Party study (38% v 61% and 27% v 47%, respectively), which might result from more intensive induction and early reintensification therapy in the ALL-BFM protocols. MRD values were the only reliable parameter to discriminate between a low and high risk of relapse (P = .02).