Title |
A Leukemia-Associated CD34/CD123/CD25/CD99+ Immunophenotype Identifies FLT3-Mutated Clones in Acute Myeloid Leukemia
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Published in |
Clinical Cancer Research, August 2015
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DOI | 10.1158/1078-0432.ccr-14-3186 |
Pubmed ID | |
Authors |
Daniela F. Angelini, Tiziana Ottone, Gisella Guerrera, Serena Lavorgna, Michela Cittadini, Francesco Buccisano, Marco De Bardi, Francesca Gargano, Luca Maurillo, Mariadomenica Divona, Nélida I. Noguera, Maria Irno Consalvo, Giovanna Borsellino, Giorgio Bernardi, Sergio Amadori, Adriano Venditti, Luca Battistini, Francesco Lo-Coco |
Abstract |
Purpose We evaluated leukemia-associated immunophenotypes (LAIP) and their correlation with fms-like tyrosine kinase 3 (FLT3) and nucleophosmin (NPM1) gene mutational status in order to contribute a better identification of patients at highest risk of relapse in AML. Bone marrow samples from 132 patients with acute myeloid leukemia (AML) were analyzed by 9-color multiparametric flow cytometry (MPFC). We confirmed the presence of the mutation in diagnostic samples and in sorted cells by conventional RT-PCR and by patient-specific RQ-PCR. Within the CD34+ve cell fraction we identified a discrete population expressing high levels of the IL-3 receptor alpha-chain (CD123) and MIC-2 (CD99) in combination with the IL-2 receptor alpha-chain (CD25). The presence of this population positively correlated with the internal tandem duplications (ITD) mutation in the FLT3 gene (r = 0.71). Receiver operating characteristics (ROC) showed that, within the CD34+ve cell fraction a percentage of CD123/CD99/CD25+ve cells ≥ 11.7% predicted FLT3-ITD mutations with a specificity and sensitivity of >90%. CD34/CD123/CD99/CD25+ve clones were also detectable at presentation in 3 patients with FLT3 wild-type/NPM1+ve AML who relapsed with FLT3-ITD/NPM1+ve AML. Quantitative real-time PCR designed at relapse for each FLT3-ITD in these three cases confirmed the presence of low copy numbers of the mutation in diagnostic samples. Our results suggest that the CD34/25/123/99+ve LAIP is strictly associated with FLT3-ITD positive cells. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 3 | 75% |
Unknown | 1 | 25% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 3 | 75% |
Scientists | 1 | 25% |
Mendeley readers
Geographical breakdown
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Unknown | 72 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 12 | 17% |
Student > Ph. D. Student | 11 | 15% |
Student > Bachelor | 9 | 13% |
Student > Doctoral Student | 6 | 8% |
Professor | 4 | 6% |
Other | 15 | 21% |
Unknown | 15 | 21% |
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Biochemistry, Genetics and Molecular Biology | 10 | 14% |
Agricultural and Biological Sciences | 7 | 10% |
Immunology and Microbiology | 3 | 4% |
Social Sciences | 1 | 1% |
Other | 1 | 1% |
Unknown | 20 | 28% |