No abstract

Loss of p53Fa tumor suppressor gene located on the short arm of chromosome 17 (band 17p13.1)Fwas detected in 105 out of 2272 (5%) adult acute myeloid leukemia (AML) patients who took part in the Study Alliance Leukemia AML96 and AML2003 multi center trials. There were 85 patients with 17p (p53) deletion with multiple aberrations and 20 patients with a 17p (p53) deletion as single aberration or with only one additional chromosomal abnormality. None of the p53-deleted patients displayed additional low-risk aberrations, like t(8;21) or inv(16). Significant positive association between p53 deletion and other high-risk factors was identified for del(5q) (Po0.001), À5 (Po0.001) and À7 (Po0.05). The molecular risk factors FLT3-ITD and NPM1 mutation showed an inverse correlation to the p53 deletion in complex aberrant patients (Po0.001). The multivariate analysis revealed p53 deletion without multiple aberrations as an independent negative prognostic factor for disease-free survival (Po0.001), relapse risk (P ¼ 0.028) and overall survival (Po0.001). Thus, the single p53 deletion should be considered as a high-risk aberration for future risk-adapted treatment strategies in AML.

Partial tandem duplication (PTD) of the MLL gene and internal tandem duplication (ITD) of the juxtamembrane region of the FLT3 receptor tyrosine kinase gene have been described in acute myeloid leukemia (AML) patients, preferentially in those with normal cytogenetics. These alterations have been associated with a poor prognosis. In our study, we analyzed the prevalence and the potential prognostic impact of these aberrations in a large unselected and well-defined cohort of 956 patients with AML. Results were correlated with cytogenetic data and clinical outcome. MLL PTD was detected by RT-PCR, subsequent nucleotide sequencing, and Southern blotting. The overall incidence was found to be 5.0% (48/956), whereas FLT3 ITD was detected in 19.2% (184/956). Sixteen cases were positive for both alterations. The rate of MLL PTD in FLT3 ITD positive patients was significantly higher than that in FLT3 ITD negative patients [16/184 (8.7%); 32/772 (4.1%); P = 0.025]. However, both aberrations were highly increased in patients with normal karyotype (MLL PTD 35/431, P = 0.004; FLT3 ITD 132/334, P < 0.001). When restricted to this subgroup, the rate of MLL PTD in patients with FLT3 mutations was not significantly increased. No statistically significant differences were detected between patients positive for MLL PTD and patients negative for MLL PTD in the rate of complete remissions or the overall survival, although we did see a significantly shorter disease-free survival in patients age 60 or younger. In conclusion, although there is an overlap in the mutational spectrum in AML with FLT3 ITD and MLL PTD mutations, our data do not support a common mechanistic basis. Although associated with inferior disease-free survival, the results of this study do not unequivocally support the notion that MLL PTD mutations represent an independent prognostic factor.

For personal use only. on May 9, 2018. by guest www.bloodjournal.org From 42. Byrd JC, Ruppert AS, Mró zek K, et al. Repetitive cycles of high-dose cytarabine benefit patients with acute myeloid leukemia and inv(16)(p13q22) or t(16;16)(p13;q22): results from CALGB 8461. patients age and no independent prognostic relevance as analyzed in 1766 MLD according to the WHO classification in AML has no correlation with http://www.bloodjournal.org/content/111/4/1855.full.html Updated information and services can be found at: (4746 articles) Clinical Trials and Observations Articles on similar topics can be found in the following Blood collections http://www.bloodjournal.org/site/misc/rights.xhtml#repub_requests Information about reproducing this article in parts or in its entirety may be found online at: http://www.bloodjournal.org/site/misc/rights.xhtml#reprints Information about ordering reprints may be found online at: http://www.bloodjournal.org/site/subscriptions/index.xhtml Information about subscriptions and ASH membership may be found online at: