Matarraz, SergioLeoz, PilarFernández, CarlosColado, EnriqueChillón, María CarmenVidriales, María BelénGonzález, MarcosRivera, DanielOsuna, Carlos SalvadorCaballero-Velázquez, TeresaVan Der Velden, VincentJongen-Lavrencic, MojcaGutiérrez, OliverBermejo, Ana YeguasAlonso, Luis GarcíaGarcía, Monique BourgeoisDe Ramón Sánchez, CristinaGarcía-Donas, GloriaMateo, Aránzazu GarcíaRecio, IsabelSánchez-Real, JavierMayado, AndreaGutiérrez, María LauraBárcena, PalomaBarrena, SusanaLópez, AntonioVan Dongen, JacquesOrfao, Alberto2023-01-252023-01-252018-03-23http://hdl.handle.net/10668/12271Severe 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.enAdolescentAdultAgedAged, 80 and overBasophilsCell LineageChildChild, PreschoolFemaleHemorrhageHumansLeukemia, Promyelocytic, AcuteMaleMiddle AgedPhenotypeYoung Adultresearch article29572500open access10.1038/s41379-018-0038-21530-0285https://www.nature.com/articles/s41379-018-0038-2.pdf