Metallothionein 1 (Mt1) Regulates Growth and Survival of DNMT3A NPM1-Mutant Acute Myeloid Leukemia
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ABSTRACT:
PROVIDER: PRJNA1090929 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28422800_1.fastq.gz | Fastqsanger.gz | |||
| SRR28422800_2.fastq.gz | Fastqsanger.gz | |||
| SRR28422801_1.fastq.gz | Fastqsanger.gz | |||
| SRR28422801_2.fastq.gz | Fastqsanger.gz | |||
| SRR28422802_1.fastq.gz | Fastqsanger.gz |
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Project description:AML with mutated NPM1 usually carries normal karyotype (NK) but it may harbor chromosomal aberrations whose significance remains unclear. We addressed this question in 631 AML patients with mutated/cytoplasmic NPM1. An abnormal karyotype (AK) was present in 93/631 cases (14.7%), the most frequent abnormalities being +8, +4, -Y, del(9q), +21. Chromosome aberrations in NPM1-mutated AML were similar to, but occurred less frequently than additional chromosome changes found in other AML with recurrent cytogenetic abnormalities according to WHO classification. Four of the 31 NPM1-mutated AML patients karyotyped at different time points had NK at diagnosis but AK at relapse: del(9q) (n=2), t(2;11) (n=1), inv(12) (n=1). NPM1-mutated AML with NK or AK showed overlapping morphological, immunophenotypic (CD34-negativity) and gene expression profile (downregulation of CD34 and upregulation of HOX genes). No difference in survival was observed among NPM1-mutated AML patients independently of whether they carried a normal or abnormal karyotype, the NPM1-mutated/FLT3-ITD negative cases showing the better prognosis. Findings in our patients point to chromosomal aberrations as secondary events, reinforce the concept that NPM1 mutation is a founder genetic lesion and indicate that NPM1-mutated AML should be clinically handled as one entity, irrespective of the karyotype. All bone marrow samples were obtained from untreated patients at the time of diagnosis. Cells used for microarray analysis were collected from the purified fraction of mononuclear cells after Ficoll density centrifugation.
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