Abstract:
Background:In addition to morphological and cytogenetic features, acute myeloid leukemias are characterized by mutations that can be used for target-therapy; also the minimal/measurable residual disease (MRD) could be an important prognostic factor. The purpose of this retrospective study was to investigate if somatic mutations could represent an additional prognostic value in respect of MRD alone. Method:At baseline, 98 patients were tested for NPM1, FLT3, and for WT1 expression; 31 for ASXL1, TET2, IDH1, IDH2, N-RAS, WT1, c-KIT, RUNX1, and DNMT3A. The same genes have been also tested after induction and consolidation. Results:Overall, 60.2% of our patients resulted mutated: 24.5% carried mutations of FLT3-ITD, 38.7% of NPM1, 48.4% of c-KIT, 25.8% of N-RAS and 19.3% of IDH2. The probability of achieving a complete response (CR) was higher for younger patients, with low ELN risk score, NPM1-mutated, with low WT1 levels, and without FLT3. The presence of additional mutations represented a poor predictive factor: only 19% of these cases achieved CR in comparison to 43% of subjects without any of it. Concerning survival, it was conditioned by a lower ELN risk score, younger age, reduction > 1 log of the NPM1 mutational burden, disappearance of FLT3 mutations and lower WT1 expression. Regarding the role of the additional mutations, they impaired the outcome of 20% of the already MRD-negative patients. Concerning the possibility of predicting relapse, we observed an increase of the NPM1 mutational burden at the time-point immediately preceding the relapse (about 2 months earlier) in 50% of subjects. Similarly concerning WT1, an increase of its expression anticipated disease recurrence in 64% of cases. Conclusions:We demonstrated that additional somatic mutations are able to impair outcome of the already MRD-negative subjects. About MRD, we suggest a prognostic role also for the WT1 expression. Finally, we considered as relevant the assessment of NPM1 quantity clearance instead of the presence/absence of mutations alone. Still remains in doubt the utility in terms of long-term prognosis of a baseline more complex mutational screening; we could hypothesize that it would be useful for those patients where other markers are not available or who reached the MRD negativity.
journal_name
Cancer Cell Intjournal_title
Cancer cell internationalauthors
Salehzadeh S,Guerrini F,Pizzano U,Grassi S,Ciabatti E,Iovino L,Buda G,Caracciolo F,Benedetti E,Orciuolo E,Pelosini M,Consani G,Carulli G,Metelli MR,Martini F,Mazziotta F,Mazzantini E,Rossi P,Tavarozzi R,Ricci F,Pedoi
10.1186/s12935-019-0807-0subject
Has Abstractpub_date
2019-04-04 00:00:00pages
83issn
1475-2867pii
807journal_volume
19pub_type
杂志文章abstract:Background:Angiogenesis plays critical roles in the progression and metastasis of malignant tumors. Gastric neuroendocrine carcinoma is an uncommon stomach cancer that is rich in blood vessels and exhibits highly malignant biological behavior with a poor prognosis. The role of CDK5RAP3 in GNEC has not been reported to ...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-019-0997-5
更新日期:2019-11-07 00:00:00
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更新日期:2019-09-09 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-015-0214-0
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journal_title:Cancer cell international
pub_type: 杂志文章,评审
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-017-0406-x
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-01474-7
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abstract:Background:Colorectal cancer (CRC) is considered as the second common death-induced cancer. More recently, association of long non-coding RNAs (lncRNAs) with CRC has been extensively investigated. Therefore, the present study was performed to determine whether lncRNA MAF BZIP Transcription Factor G Antisense RNA 1 (MAF...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-01485-4
更新日期:2020-10-19 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/1475-2867-14-19
更新日期:2014-03-01 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/1475-2867-12-44
更新日期:2012-11-07 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-01541-z
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-01537-9
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-019-0818-x
更新日期:2019-04-24 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章,评审
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更新日期:2018-11-14 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-018-0682-0
更新日期:2018-11-20 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-01483-6
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journal_title:Cancer cell international
pub_type: 杂志文章
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-018-0638-4
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-019-0761-x
更新日期:2019-02-28 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章,评审
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journal_title:Cancer cell international
pub_type: 杂志文章
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journal_title:Cancer cell international
pub_type: 杂志文章,评审
doi:10.1186/s12935-020-01535-x
更新日期:2020-09-15 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章,收录出版
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更新日期:2020-08-26 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/1475-2867-13-30
更新日期:2013-03-28 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-015-0183-3
更新日期:2015-04-01 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/1475-2867-3-4
更新日期:2003-03-25 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-01461-y
更新日期:2020-08-03 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/1475-2867-11-6
更新日期:2011-03-10 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-019-1092-7
更新日期:2020-03-12 00:00:00
abstract::miRNAs, a major class of small noncoding RNAs approximately 18-25 nucleotides in length, function by repressing the expression of target genes through binding to complementary sequences in the 3'-UTRs of target genes. Emerging evidence has highlighted their important roles in numerous diseases, including human cancers...
journal_title:Cancer cell international
pub_type: 杂志文章,评审
doi:10.1186/s12935-019-0984-x
更新日期:2019-10-07 00:00:00