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.

Cancer Research Center Salamanca

Cancer Research Center Salamanca Spain

Center of Biostatistics for Clinical Epidemiology Dipartimento di Medicina e Chirurgia Università degli Studi Milano Bicocca Monza

Centro Tettamanti Fondazione IRCCS San Gerardo dei Tintori Monza

Centro Tettamanti Fondazione IRCCS San Gerardo dei Tintori Monza Italy

CLIP Department of Pediatric Hematology and Oncology 2nd Faculty of Medicine Charles University and University Hospital Motol Prague Czech Republic

Department of Immunohematology and Blood Transfusion Leiden

Department of Immunology Erasmus MC University Medical Center Rotterdam Rotterdam

Department of Laboratory Medicine Ghent University Hospital Ghent

Department of Pediatric Hematology and Oncology IRCCS Ospedale Pediatrico Bambino Gesu' Sapienza University of Rome

Department of Pediatric Hematology and Oncology Medical University of Silesia Zabrze

Department of Pediatrics Federal University of Rio de Janeiro Rio de Janeiro

Department of Pediatrics Fondazione IRCCS San Gerardo dei Tintori Monza

Dipartimento di Medicina e Chirurgia Università degli Studi Milano Bicocca Monza

Dipartimento di Salute della Donna e del Bambino Clinica di Oncoematologia Pediatrica Azienda Ospedale Università di Padova Padua

Hematology Laboratory CHU de Saint Etienne Saint Etienne Cedex

Institute for Laboratory Medicine Kantonsspital Aarau AG Aarau

Pediatric Oncology and Hematology Unit 'Lalla Seràgnoli' IRCCS Azienda Ospedaliero Universitaria di Bologna Bologna

Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands

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$a Phenotypic profiling of CD34+ cells by advanced flow cytometry improves diagnosis of juvenile myelomonocytic leukemia / $c C. Bugarin, L. Antolini, C. Buracchi, S. Matarraz, TA. Coliva, VH. Van der Velden, T. Szczepanski, ES. Da Costa, A. Van der Sluijs, M. Novakova, E. Mejstrikova, S. Nierkens, FV. De Mello, P. Fernandez, C. Aanei, Ł. Sędek, L. Strocchio, R. Masetti, L. Sainati, J. Philippé, MG. Valsecchi, F. Locatelli, JJM. Van Dongen, A. Biondi, A. Orfao, G. Gaipa

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$a 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.

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