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Terminal deoxynucleotidyl transferase (TdT) expression is associated with FLT3-ITD mutations in Acute Myeloid Leukemia
- Source :
- Leukemia Research. 99:106462
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- The terminal deoxynucleotidyl transferase (TdT) is a DNA polymerase expressed in acute myeloid leukemias (AMLs), where it may be involved in the generation of NPM1 and FLT3-ITD mutations. We studied the correlations between TdT expression and FLT3-ITD or NPM1 mutations in primary AML samples, and the impact on patients' survival. TdT expression was analyzed in 143 adult AML patients by flow cytometry as percentage of positivity and mean fluorescence intensity (MFI) on blasts. TdT was positive in 49 samples (34.2%), with a median of 48% TdT-positivity (range 7-98) and a median MFI of 2.70 (range 1.23-30.54). FLT3-ITD and NPM1 mutations were present in 24 (16.7%) and 34 (23.7%) cases, respectively. Median TdT expression on blasts was significantly higher in FLT3-ITD+, as compared with FLT3-ITD- AMLs (median 8% vs 0% respectively, p = 0.035). NPM1 mutational status, FLT3-ITD allelic ratio, karyotype, and ELN risk groups, did not correlate with TdT expression or MFI on blasts. TdT + patients had poorer survival as compared to TdT-, but this result was not confirmed by the multivariable analysis, where ELN risk stratification as well as age and type of treatment remained independent prognostic factors for OS. In summary, our results support the possible implication of TdT enzyme in the generation of FLT3-ITD mutations in AML.
- Subjects :
- Adult
DNA Replication
Male
endocrine system
Cancer Research
NPM1
overall survival
Kaplan-Meier Estimate
acute myeloid leukemia
FLT3-ITD mutations
Flow cytometry
Young Adult
03 medical and health sciences
0302 clinical medicine
DNA Nucleotidylexotransferase
hemic and lymphatic diseases
medicine
Humans
Mutational status
Aged
Aged, 80 and over
medicine.diagnostic_test
business.industry
Mean fluorescence intensity
Nuclear Proteins
Myeloid leukemia
Karyotype
DNA, Neoplasm
Hematology
Middle Aged
Settore MED/15
Molecular biology
Neoplasm Proteins
terminal deoxynucleotidyl transferase
Leukemia, Myeloid, Acute
stomatognathic diseases
fms-Like Tyrosine Kinase 3
Oncology
Terminal deoxynucleotidyl transferase
Mutagenesis
030220 oncology & carcinogenesis
Female
business
Nucleophosmin
“filler” sequences
psychological phenomena and processes
030215 immunology
Flt3 itd
Subjects
Details
- ISSN :
- 01452126
- Volume :
- 99
- Database :
- OpenAIRE
- Journal :
- Leukemia Research
- Accession number :
- edsair.doi.dedup.....c860dedfbd6a9f7a3ebc1345f3903f81