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Normal Cytogenetics (normal + cytogenetics)

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Medical Sciences	100%

Selected Abstracts

Comparative analysis of MLL partial tandem duplication and FLT3 internal tandem duplication mutations in 956 adult patients with acute myeloid leukemia

GENES, CHROMOSOMES AND CANCER, Issue 3 2003
Christine Steudel
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. © 2003 Wiley-Liss, Inc. [source]

C/EBPA gene mutation and C/EBPA promoter hypermethylation in acute myeloid leukemia with normal cytogenetics,,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 6 2010
Ying Lu
In the current study, we investigated C/EBPA gene mutations and promoter hypermethylation in a series of 53 patients with CN-AML. In addition, we also analyzed two other frequent mutations (FLT3/ITD and NPM1) in these patients and correlated them with C/EBPA gene alterations. 13/53 patients were FLT3/ITD+/NPM1- , 11/53 patients were FLT3/ITD+/NPM1+, 9/53 patients were FLT3/ITD-/NPM1+, and 20/53 patients were FLT3/ITD-/NPM1- . Four of 53 cases displayed C/EBPA mutations, whereas 49 cases had only C/EBPA wild-type alleles. Of the four positive cases, three patients had N-terminal mutations only, whereas one patient had mutations in both the N- and C-terminal region. Two of the four positive cases also harbored both FLT3/ITD and NPM1 mutation simultaneously, whereas the other two patients had neither FLT3/ITD nor NPM1 mutations. Furthermore, 7/53 cases displayed C/EBPA promoter hypermethylation. Interestingly, they were all in CN-AML cases without FLT3/ITD or NPM1 mutations. None of the seven patients with C/EBPA promoter hypermethylation showed C/EBPA mutation. In conclusion, C/EBPA mutation and promoter hypermethylation can be detected at a relatively low frequency in de novo CN-AML patients, suggesting they may contribute to leukemogenesis. C/EBPA mutation appears to be seen in "high-risk" AML (FLT3/ITD+/NPM1+; FLT3/ITD+/NPM1- or FLT3/ITD-/NPM1- ), while C/EBPA hypermethylation appears to be more common in AML with FLT3/ITD - /NPM1 - and is not associated with C/EBPA mutation. Am. J. Hematol. 2010. © 2010 Wiley-Liss, Inc. [source]

Elevated AF1q expression is a poor prognostic marker for adult acute myeloid leukemia patients with normal cytogenetics,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2009
Crawford J. Strunk
Nearly half of the patients with newly diagnosed acute myeloid leukemia have normal cytogenetics (NC-AML) and are classified as intermediate risk, but their 5-year overall survival (OS) ranges from 24 to 42%. Therefore, molecular biomarkers to identify poor-risk patients are needed. Elevated AF1q expression in the absence of specific poor cytogenetics is associated with poor outcomes in pediatric patients with AML and adult patients with myelodysplastic syndrome. We examined AF1q expression in 290 patients with NC-AML. We found that patients with low AF1q (n = 73) expression (AF1qlow) have better OS (P = 0.026), disease-free survival (P = 0.1), and complete remission rate (P = 0.06) when compared with patients with high AF1q expression (AF1qhighn = 217). The patients with AF1qhigh had significantly greater incidence of concurrent tyrosine kinase3 internal tandem duplication. A subgroup of the patients with AF1qhigh who received allogeneic stem cell transplantation (SCT) had a significant better relapse-free survival when compared with patients who received chemotherapy/autologous SCT (P = 0.04). This study suggests that high AF1q expression is a poor prognostic marker for adult patients with NC-AML. [source]