Clinical Oncohematology · 2016
Relation between Genomic DNA Breakpoints in MLL Gene and Treatment Outcome in Infants with Acute Leukemia
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Grigorii Anatol’evich Tsaur, C. Meyer, T. O. Riger, A. M. Kustanovich, E. V. Fleischman, Yu. V. Ol’shanskaya, A. M. Popov, O. I. Sokova, E. A. Matveeva, O. V. Nikulina, A. E. Drui, O. R. Arakaev, O. V. Streneva, S. A. Rumyantsev, E. V. Shorikov, A. G. Solodovnikov, L. I. Savel’ev, R. Marschalek, L. G. Fechina
Аннотация
Aim. To evaluate the relation between genomic DNA breakpoints in MLL and translocation partner genes (TPG) and clinical parameters of infant AL. Methods. 68 infants (29 boys and 39 girls with median age of 4.8 mo) with MLL-rearranged acute lymphoblastic leukemia (ALL) (n = 46), acute myeloid leukemia (AML) (n = 20) and mixed phenotype acute leukemia (MPAL) (n = 2) were included in the current study. Results. 5-year EFS was significantly lower in patients with breakpoints in intron 11 (n = 29) in comparison to patients with breakpoint localized from intron 7 to exon 11 (n = 17) (0.16 ± 0.07 vs 0.38 ± 0.14, p = 0.039). While cumulative incidence of relapse was remarkably higher in the first group of patients (0.74 ± 0.09 vs 0.52 ± 0.17, p = 0.045). Although in Cox regression model including breakpoint location in intron 11 together with age, immunophenotype, initial white blood cell count, initial CNS involvement, type of MLL rearrangements, absolute blast number at day 8 of dexamethasone profase, minimal residual disease (MRD) at time point 4 (TP4) of MLL-Baby protocol, the only significant covariate was the presence of MRD at TP4 (HR 5.994, 95% CI 2.209–16.263, p