IKZF1 gene deletions have been associated with a poor outcome in pediatric precursor B-cell acute lymphoblastic leukemia. To assess the prognostic relevance of IKZF1 deletions for patients treated on Berlin-Frankfurt-Münster Study Group trial ALL-BFM 2000, we screened 694 diagnostic acute lymphoblastic leukemia samples by Multiplex Ligation-dependent Probe Amplification. Patients whose leukemic cells bore IKZF1 deletions had a lower 5-year event-free survival (0.69±0.05 vs. 0.85±0.01; P<0.0001) compared to those without, mainly due to a higher cumulative incidence of relapses (0.21±0.04 vs. 0.10±0.01; P=0.001). Although IKZF1 deletions were significantly associated with the P2RY8-CRLF2 rearrangement, their prognostic value was found to be independent from this association. Thus, IKZF1 deletion is an independent predictor of treatment outcome and a strong candidate marker for integration in future treatment stratification strategies on ALL-BFM protocols.
Clinicaltrials.gov identifier: NCT00430118
ABSTRACTConsecutively enrolled patients from the ALL-BFM 2000 study population with sufficient spare leukemic DNA available were included in our present study (Online Supplementary Table S1). BM or peripheral blood specimens had to contain more than 80% blasts, as assessed morphologically before gradient centrifugation.
The cAMP synthesis by fetal rat thyroids is stimulated in vitro by thyrotropin (TSH) or forskolin during the 5 last days of intrauterine life. The effects are TSH- or forskolin-dose-dependent with equal responses to 20 mlU·ml––1 TSH or to 1 μM forskolin. The magnitude of the responses to TSH or to forskolin decreases significantly as the fetus is ageing. Since forskolin effects bypass hormone receptors, the adenylate cyclase activity can be concluded to decrease during the end of gestation probably in relation with thyroid iodine accumulation. The responses to TSH and forskolin becoming synergic between 19½ and 21½ days indicate modifications of adenylate cyclase properties probably related to some maturation of the enzyme.
Decapitation performed at days 17-18 leads to a drastic drop (82%) in blood TSH of 19 and 21-day-old rat fetuses below the mother's level. 125I-TSH injected at 21 days into the mother's bloodstream is not found in fetal blood. The fetal hypophysis is the main source of fetal plasmatic TSH.
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