Tyrosine kinase fusion genes in pediatric BCR-ABL1-like acute lymphoblastic leukemia

Approximately 15% of pediatric B cell precursor acute lymphoblastic leukemia (BCP-ALL) is characterized by gene expression similar to that of BCR-ABL1-positive disease and unfavorable prognosis. This BCR-ABL1-like subtype shows a high frequency of B-cell development gene aberrations and tyrosine kinase-activating lesions. To evaluate the clinical significance of tyrosine kinase gene fusions in children with BCP-ALL, we studied the frequency of recently identified tyrosine kinase fusions, associated genetic features, and prognosis in a representative Dutch/German cohort. We identified 14 tyrosine kinase fusions among 77 BCR-ABL1-like cases (18%) and none among 76 non-BCR-ABL1-like B-other cases. Novel exon fusions were identified for RCSD1-ABL2 and TERF2-JAK2. JAK2 mutation was mutually exclusive with tyrosine kinase fusions and only occurred in cases with high CRLF2 expression. The non/late response rate and levels of minimal residual disease in the fusion-positive BCR-ABL1- like group were higher than in the non-BCR-ABL1-like B-others (p < 0.01), and also higher, albeit not statistically significant, compared with the fusion-negative BCRABL1- like group. The 8-year cumulative incidence of relapse in the fusion-positive BCR-ABL1-like group (35%) was comparable with that in the fusion-negative BCRABL1- like group (35%), and worse than in the non-BCR-ABL1-like B-other group (17%, p=0.07). IKZF1 deletions, predominantly other than the dominant-negative isoform and full deletion, co-occurred with tyrosine kinase fusions. This study shows that tyrosine kinase fusion-positive cases are a high-risk subtype of BCP-ALL, which warrants further studies with specific kinase inhibitors to improve outcome

INCLUSIVE PHOTON PRODUCTION IN P A AND A-A COLLISIONS AT 200-GEV/u

Inclusive photonp ⊥ spectra were measured with 200 GeV/u proton,16O and32S beams on W and Pt targets, using a conversion method. The measurement of charged pions in the same apparatus allows a comparison of the γ data with the expected γ's from hadronic decays π0, η, η', ω). In all data sets, no deviation from the expected shape is observed in the range of 0.10.1 GeV/c andp ⊥>0.6 GeV/c