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    Diagnostic criteria for juvenile myelomonocytic leukemia (JMML) are currently well defined, however in some patients diagnosis still remains a challenge. Flow cytometry is a well established tool for diagnosis and follow-up of hematological malignancies, nevertheless it is not routinely used for JMML diagnosis. Herewith, we characterized the CD34+ hematopoietic precursor cells collected from 31 children with JMML using a combination of standardized EuroFlow antibody panels to assess the ability to discriminate JMML cells from normal/reactive bone marrow cell as controls (n=29) or from cells of children with other hematological diseases mimicking JMML (n=9). CD34+ precursors in JMML showed markedly reduced B-cell and erythroid-committed precursors compared to controls, whereas monocytic and CD7+ lymphoid precursors were significantly expanded. Moreover, aberrant immunophenotypes were consistently present in CD34+ precursors in JMML, while they were virtually absent in controls. Multivariate logistic regression analysis showed that combined assessment of the number of CD34+CD7+ lymphoid precursors and CD34+ aberrant precursors or erythroid precursors had a great potential in discriminating JMMLs versus controls. Importantly our scoring model allowed highly efficient discrimination of truly JMML versus patients with JMML-like diseases. In conclusion, we show for the first time that CD34+ precursors from JMML patients display a unique immunophenotypic profile which might contribute to a fast and accurate diagnosis of JMML worldwide by applying an easy to standardize single eight-color antibody combination.


    Cristina Bugarin, Laura Antolini, Chiara Buracchi, Sergio Matarraz, Tiziana Angela Coliva, Vincent H Van der Velden, Tomasz Szczepanski, Elaine Sobral Da Costa, Alita Van der Sluijs, Michaela Novakova, Ester Mejstrikova, Stefan Nierkens, Fabiana Vieira De Mello, Paula Fernandez, Carmen Aanei, Łukasz Sędek, Luisa Strocchio, Riccardo Masetti, Laura Sainati, Jan Philippé, Maria Grazia Valsecchi, Franco Locatelli, Jacques J M Van Dongen, Andrea Biondi, Alberto Orfao, Giuseppe Gaipa. Phenotypic profiling of CD34+ cells by advanced flow cytometry improves diagnosis of juvenile myelomonocytic leukemia. Haematologica. 2024 Feb 01;109(2):521-532

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    PMID: 37534527

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