Basophil-lineage commitment in acute promyelocytic leukemia predicts for severe bleeding after starting therapy

Severe hemorrhagic events occur in a significant fraction of acute promyelocytic leukemia patients, either at presentation and/or early after starting therapy, leading to treatment failure and early deaths. However, identification of independent predictors for high-risk of severe bleeding at diagnos...

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Published in:	Modern pathology Vol. 31; no. 8; pp. 1318 - 1331
Main Authors:	Matarraz, Sergio, Leoz, Pilar, Fernández, Carlos, Colado, Enrique, Chillón, María Carmen, Vidriales, María Belén, González, Marcos, Rivera, Daniel, Osuna, Carlos Salvador, Caballero-Velázquez, Teresa, Van Der Velden, Vincent, Jongen-Lavrencic, Mojca, Gutiérrez, Oliver, Bermejo, Ana Yeguas, Alonso, Luis García, García, Monique Bourgeois, De Ramón Sánchez, Cristina, García-Donas, Gloria, Mateo, Aránzazu García, Recio, Isabel, Sánchez-Real, Javier, Mayado, Andrea, Gutiérrez, María Laura, Bárcena, Paloma, Barrena, Susana, López, Antonio, Van Dongen, Jacques, Orfao, Alberto
Format:	Journal Article
Language:	English
Published:	New York Nature Publishing Group US 01-08-2018 Elsevier Limited
Subjects:	13/31 14/63 38/32 38/77 692/53/2423 692/699/67/1990/283/1897 Acute promyeloid leukemia Adolescent Adult Aged Aged, 80 and over Basophils - pathology Bleeding Bone marrow CD22 antigen CD34 antigen CD7 antigen Cell Lineage Child Child, Preschool Diagnosis Female Fibrinogen Hemorrhage Hemorrhage - etiology Humans Laboratory Medicine Leukemia Leukemia, Promyelocytic, Acute - complications Leukemia, Promyelocytic, Acute - pathology Lymphocyte receptors Male Medicine Medicine & Public Health Middle Aged Multivariate analysis Pathology Patients Phenotype Phenotypes Promyeloid leukemia Young Adult
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Summary:	Severe hemorrhagic events occur in a significant fraction of acute promyelocytic leukemia patients, either at presentation and/or early after starting therapy, leading to treatment failure and early deaths. However, identification of independent predictors for high-risk of severe bleeding at diagnosis, remains a challenge. Here, we investigated the immunophenotype of bone marrow leukemic cells from 109 newly diagnosed acute promyelocytic leukemia patients, particularly focusing on the identification of basophil-related features, and their potential association with severe bleeding episodes and patient overall survival. From all phenotypes investigated on leukemic cells, expression of the CD203c and/or CD22 basophil-associated markers showed the strongest association with the occurrence and severity of bleeding ( p ≤ 0.007); moreover, aberrant expression of CD7, coexpression of CD34 + /CD7 + and lack of CD71 was also more frequently found among patients with (mild and severe) bleeding at baseline and/or after starting treatment ( p ≤ 0.009). Multivariate analysis showed that CD203c expression (hazard ratio: 26.4; p = 0.003) and older age (hazard ratio: 5.4; p = 0.03) were the best independent predictors for cumulative incidence of severe bleeding after starting therapy. In addition, CD203c expression on leukemic cells (hazard ratio: 4.4; p = 0.01), low fibrinogen levels (hazard ratio: 8.8; p = 0.001), older age (hazard ratio: 9.0; p = 0.002), and high leukocyte count (hazard ratio: 5.6; p = 0.02) were the most informative independent predictors for overall survival. In summary, our results show that the presence of basophil-associated phenotypic characteristics on leukemic cells from acute promyelocytic leukemia patients at diagnosis is a powerful independent predictor for severe bleeding and overall survival, which might contribute in the future to (early) risk-adapted therapy decisions.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0893-3952 1530-0285
DOI:	10.1038/s41379-018-0038-2