Phenotypic profiling of CD34+ cells by advanced flow cytometry improves diagnosis of juvenile myelomonocytic leukemia
Haematologica, vol. 109, pp. 521–532
Abstract
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.
Authors 26
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Affiliation as printed
Centro Tettamanti, Fondazione IRCCS San Gerardo dei Tintori, Monza (MB)
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Affiliation as printed
Center of Biostatistics for Clinical Epidemiology, Dipartimento di Medicina e Chirurgia, Università degli Studi Milano-Bicocca, Monza (MB)
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Affiliation as printed
Centro Tettamanti, Fondazione IRCCS San Gerardo dei Tintori, Monza (MB)
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Universidad de Salamanca · Instituto de Investigación Biomédica de Salamanca · Centro de Investigación del Cáncer · Centro de Investigación Biomédica en Red de Cáncer · Instituto de Biología Molecular y Celular del Cáncer de Salamanca
Affiliation as printed
Cancer Research Center (IBMCC-CSIC), Department of Medicine and Cytometry Service (NUCLEUS), University of Salamanca, CIBERONC and Institute of Biomedical Research of Salamanca (IBSAL), Salamanca
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Affiliation as printed
Department of Pediatrics, Fondazione IRCCS San Gerardo dei Tintori, Monza (MB)
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Affiliation as printed
Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam
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Affiliation as printed
Department of Pediatric Hematology and Oncology, Medical University of Silesia (SUM), Zabrze
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Universidade Federal do Rio de Janeiro
Affiliation as printed
Department of Pediatrics, Federal University of Rio de Janeiro, Rio de Janeiro
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Alita van der Sluijs Aachen Department of Immunohematology and Blood Transfusion (IHB) Leiden University Medical Center (LUMC)
Leiden University Medical Center
Affiliation as printed
Department of Immunohematology and Blood Transfusion (IHB) Leiden University Medical Center (LUMC), Leiden
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Charles University · University Hospital in Motol
Affiliation as printed
CLIP-Department of Pediatric Hematology and Oncology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
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Charles University · University Hospital in Motol
Affiliation as printed
CLIP-Department of Pediatric Hematology and Oncology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
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Affiliation as printed
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
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Universidade Federal do Rio de Janeiro
Affiliation as printed
Department of Pediatrics, Federal University of Rio de Janeiro, Rio de Janeiro
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Affiliation as printed
Institute for Laboratory Medicine, Kantonsspital Aarau AG, Aarau
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Centre Hospitalier Universitaire de Saint-Étienne
Affiliation as printed
Hematology Laboratory CHU de Saint-Etienne, Saint-Etienne, Cedex 2
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Affiliation as printed
Department of Pediatric Hematology and Oncology, Medical University of Silesia (SUM), Zabrze
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Bambino Gesù Children's Hospital · Sapienza University of Rome
Affiliation as printed
Department of Pediatric Hematology and Oncology IRCCS Ospedale Pediatrico Bambino Gesu', Sapienza University of Rome
Department of Pediatric Hematology and Oncology IRCCS Ospedale Pediatrico Bambino Gesu’, Sapienza University of Rome
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IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola
Affiliation as printed
Pediatric Oncology and Hematology Unit 'Lalla Seràgnoli', IRCCS Azienda Ospedaliero- Universitaria di Bologna, Bologna
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University of Padua · Azienda Ospedale - Università Padova
Affiliation as printed
Dipartimento di Salute della Donna e del Bambino, Clinica di Oncoematologia Pediatrica, Azienda Ospedale Università di Padova, Padua
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Affiliation as printed
Department of Laboratory Medicine, Ghent University Hospital, Ghent
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Affiliation as printed
Center of Biostatistics for Clinical Epidemiology, Dipartimento di Medicina e Chirurgia, Università degli Studi Milano-Bicocca, Monza (MB). grazia.valsecchi@unimib.it
Center of Biostatistics for Clinical Epidemiology, Dipartimento di Medicina e Chirurgia, Università degli Studi Milano-Bicocca, Monza (MB)
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Bambino Gesù Children's Hospital · Sapienza University of Rome
Affiliation as printed
Department of Pediatric Hematology and Oncology IRCCS Ospedale Pediatrico Bambino Gesu', Sapienza University of Rome
Department of Pediatric Hematology and Oncology IRCCS Ospedale Pediatrico Bambino Gesu’, Sapienza University of Rome
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Jacques J. M. van Dongen Aachen Department of Immunohematology and Blood Transfusion (IHB) Leiden University Medical Center (LUMC)
Universidad de Salamanca · Leiden University Medical Center · Instituto de Investigación Biomédica de Salamanca · Centro de Investigación del Cáncer · Centro de Investigación Biomédica en Red de Cáncer · Instituto de Biología Molecular y Celular del Cáncer de Salamanca
Affiliation as printed
Cancer Research Center (IBMCC-CSIC), Department of Medicine and Cytometry Service (NUCLEUS), University of Salamanca, CIBERONC and Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain; Department of Immunohematology and Blood Transfusion (IHB) Leiden University Medical Center (LUMC), Leiden
Cancer Research Center (IBMCC-CSIC), Department of Medicine and Cytometry Service (NUCLEUS), University of Salamanca, CIBERONC and Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain
Department of Immunohematology and Blood Transfusion (IHB) Leiden University Medical Center (LUMC), Leiden
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Affiliation as printed
Centro Tettamanti, Fondazione IRCCS San Gerardo dei Tintori, Monza (MB), Italy; Dipartimento di Medicina e Chirurgia, Università degli Studi Milano-Bicocca, Monza (MB). andrea.biondi@unimib.it
Centro Tettamanti, Fondazione IRCCS San Gerardo dei Tintori, Monza (MB), Italy
Dipartimento di Medicina e Chirurgia, Università degli Studi Milano-Bicocca, Monza (MB)
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Universidad de Salamanca · Instituto de Investigación Biomédica de Salamanca · Centro de Investigación del Cáncer · Centro de Investigación Biomédica en Red de Cáncer · Instituto de Biología Molecular y Celular del Cáncer de Salamanca
Affiliation as printed
Cancer Research Center (IBMCC-CSIC), Department of Medicine and Cytometry Service (NUCLEUS), University of Salamanca, CIBERONC and Institute of Biomedical Research of Salamanca (IBSAL), Salamanca
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Affiliation as printed
Centro Tettamanti, Fondazione IRCCS San Gerardo dei Tintori, Monza (MB)
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