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Immunophenotypic Analysis of Acute Megakaryoblastic Leukemia: A EuroFlow Study

N. Brouwer, S. Matarraz, S. Nierkens, M. Hofmans, M. Nováková, ES. da Costa, P. Fernandez, AE. Bras, FV. de Mello, E. Mejstrikova, J. Philippé, GE. Grigore, CE. Pedreira, JJM. van Dongen, A. Orfao, VHJ. van der Velden, . On Behalf Of The EuroFlow...

. 2022 ; 14 (6) : . [pub] 20220321

Language English Country Switzerland

Document type Journal Article

Grant support
E26/200.840/2021-CNE Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro
306258/2019-6 National Council for Scientific and Technological Development
NU20J-07-00028 Ministry of Health of the Czech Republic

Acute megakaryoblastic leukemia (AMKL) is a rare and heterogeneous subtype of acute myeloid leukemia (AML). We evaluated the immunophenotypic profile of 72 AMKL and 114 non-AMKL AML patients using the EuroFlow AML panel. Univariate and multivariate/multidimensional analyses were performed to identify most relevant markers contributing to the diagnosis of AMKL. AMKL patients were subdivided into transient abnormal myelopoiesis (TAM), myeloid leukemia associated with Down syndrome (ML-DS), AML-not otherwise specified with megakaryocytic differentiation (NOS-AMKL), and AMKL-other patients (AML patients with other WHO classification but with flowcytometric features of megakaryocytic differentiation). Flowcytometric analysis showed good discrimination between AMKL and non-AMKL patients based on differential expression of, in particular, CD42a.CD61, CD41, CD42b, HLADR, CD15 and CD13. Combining CD42a.CD61 (positive) and CD13 (negative) resulted in a sensitivity of 71% and a specificity of 99%. Within AMKL patients, TAM and ML-DS patients showed higher frequencies of immature CD34+/CD117+ leukemic cells as compared to NOS-AMKL and AMKL-Other patients. In addition, ML-DS patients showed a significantly higher expression of CD33, CD11b, CD38 and CD7 as compared to the other three subgroups, allowing for good distinction of these patients. Overall, our data show that the EuroFlow AML panel allows for straightforward diagnosis of AMKL and that ML-DS is associated with a unique immunophenotypic profile.

Biomedical Research Networking Centre Consortium of Oncology Instituto de Salud Carlos 3 28029 Madrid Spain

Centro de Investigación del Cancer Department of Medicine University of Salamanca 37007 Salamanca Spain

CLIP Department of Pediatric Hematology and Oncology 2nd Medical Faculty Charles University and University Hospital Motol 5 Uvalu 84 15006 Prague Czech Republic

CSIC University of Salamanca) Cytometry Service NUCLEUS Department of Medicine University of Salamanca Paseo de la Universidad de Coimbra s n Campus Miguel de Unamuno 37007 Salamanca Spain

Cytognos SL Carretera de Madrid Km 0 Nave 9 Pol La Serna 37900 Salamanca Spain

Department of Diagnostic Sciences Ghent University C Heymanslaan 10 9000 Ghent Belgium

Department of Immunology Leiden University Medical Center Albinusdreef 2 2333 ZA Leiden The Netherlands

Department of Laboratory Medicine Ghent University Hospital Corneel Heymanslaan 10 9000 Ghent Belgium

Institute for Laboratory Medicine Kantonsspital Aarau AG Tellstrasse 25 5001 Aarau Switzerland

Institute of Pediatrics R Bruno Lobo 50 Cidade Universitária Rio de Janeiro RJ 21941 912 Brazil

Laboratory Medical Immunology Department of Immunology Erasmus MC University Medical Center Rotterdam Wytemaweg 80 3015 CN Rotterdam The Netherlands

Princess Máxima Center for Pediatric Oncology Heidelberglaan 25 3584 CS Utrecht The Netherlands

Systems and Computing Department COPPE Federal University of Rio de Janeiro Rio de Janeiro RJ 21941 594 Brazil

Translational and Clinical Research Program Centro de Investigación del Cáncer (IBMCC

References provided by Crossref.org

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$a Acute megakaryoblastic leukemia (AMKL) is a rare and heterogeneous subtype of acute myeloid leukemia (AML). We evaluated the immunophenotypic profile of 72 AMKL and 114 non-AMKL AML patients using the EuroFlow AML panel. Univariate and multivariate/multidimensional analyses were performed to identify most relevant markers contributing to the diagnosis of AMKL. AMKL patients were subdivided into transient abnormal myelopoiesis (TAM), myeloid leukemia associated with Down syndrome (ML-DS), AML-not otherwise specified with megakaryocytic differentiation (NOS-AMKL), and AMKL-other patients (AML patients with other WHO classification but with flowcytometric features of megakaryocytic differentiation). Flowcytometric analysis showed good discrimination between AMKL and non-AMKL patients based on differential expression of, in particular, CD42a.CD61, CD41, CD42b, HLADR, CD15 and CD13. Combining CD42a.CD61 (positive) and CD13 (negative) resulted in a sensitivity of 71% and a specificity of 99%. Within AMKL patients, TAM and ML-DS patients showed higher frequencies of immature CD34+/CD117+ leukemic cells as compared to NOS-AMKL and AMKL-Other patients. In addition, ML-DS patients showed a significantly higher expression of CD33, CD11b, CD38 and CD7 as compared to the other three subgroups, allowing for good distinction of these patients. Overall, our data show that the EuroFlow AML panel allows for straightforward diagnosis of AMKL and that ML-DS is associated with a unique immunophenotypic profile.
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