IMMUNOTHROMBOTIC PROFILE OF CELLS AND HEMOSTATIC PROFILE IN PATIENTS WITH ACUTE PROMYELOCYTIC LEUKEMIA THROUGH UNBIASED BIOINFORMATIC ANALYSIS OF MULTIPARAMETRIC FLOW CYTOMETRY
- 1Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil
Abstract
Background: Acute Promyelocytic Leukemia (APL) is a subtype of acute myeloid leukemia with increased risk of acute hemorrhagic and thrombotic complications during the induction phase. The mechanisms by which hemostasis is activated in these patients is not completely understood. Aim: Here we investigated the association between the phenotype of myeloblasts assessed using an unbiased analytical approach with laboratory and clinical markers of disease severity in APL. Methods: Clinical and laboratory data from 36 patients newly diagnosed with APL were included in this cohort. Both peripheral blood (PB: n = 6) and bone marrow (BM; n = 30) samples, obtained at diagnosis, were used for flow cytometry (FC) analyzed using the following panels: i) ALOT: cyCD79a (PE), CD19 (PE-Cy-7), CD34 (PerCP-Cy5.5), CD3 (APC-H7), CD7 (APC), cyCD3 (V450) CD45 (V500) and cyMPO (FITC); ii) AML1: CD34 (PerCP-Cy5.5), CD13 (PE), CD45 (V500) and CD16 (FITC); iii) AML2: CD34 (PerCP-Cy5.5), CD14 (APC-H7), CD64 (PE), CD117 (PE-Cy7), CD45 (V500), HLA-DR (V450) and CD35 (FITC). In addition to classical FC analytical protocols, raw files were used in an unbiased bioinformatic analysis based on the individual expression profile of each cell, capable of identifying different expression signatures. Statistical analysis between groups was made with Mann-Whitney test and correlation with Spearman test, both considering a confidence interval of 95%. All analysis was performed in R Studio (v. 2026) using unsupflowhelper and flowCore packages. Results: Based on the expression signature derived from our unbiased analysis, the frequency of Myeloblast CD34high was higher in patients with CNS bleeding, whereas the frequency of mature hematopoietic cells and lymphocytes was associated with better survival. aPTT was positively correlated with Myeloblast CD34pos counts (rho = 0.48, p = 0.02), while no correlation was observed with prothrombin time, fibrinogen and platelet counts. Discussion and conclusion: Our unbiased analytical approach allows the identification of discrete populations that could be missed by conventional FC. Using this strategy, we were able to identify an association between Myeloblast CD34high and adverse outcomes, as well as between the presence of mature cells and more favorable prognosis during first induction. Reduction of mature B cells was associated with early mortality, while the association between aPTT with CD34pos myeloblasts suggests a role of these cells in coagulation activation, but additional studies are warranted to refine this hypothesis.
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BibTeX
@article{silvajunior2026immunothrombotic,
title = {{IMMUNOTHROMBOTIC PROFILE OF CELLS AND HEMOSTATIC PROFILE IN PATIENTS WITH ACUTE PROMYELOCYTIC LEUKEMIA THROUGH UNBIASED BIOINFORMATIC ANALYSIS OF MULTIPARAMETRIC FLOW CYTOMETRY}},
author = {Alexander Leonardo SILVA-JUNIOR and Camilla Maria de Alencar SARAIVA and Carla Roberta Peachazepi MORAES and Bruno Kosa Lino DUARTE and Gislaine Borba OLIVEIRA and Katia Borgia Barbosa PAGNANO and Herton Luiz Alves SALES FILHO and Erich Vinicius DE PAULA},
journal = {Hematology, Transfusion and Cell Therapy},
year = {2026},
month = oct,
doi = {10.1016/j.htct.2026.107424},
url = {https://doi.org/10.1016/j.htct.2026.107424},
note = {CC BY},
}
RIS
TY - JOUR
TI - IMMUNOTHROMBOTIC PROFILE OF CELLS AND HEMOSTATIC PROFILE IN PATIENTS WITH ACUTE PROMYELOCYTIC LEUKEMIA THROUGH UNBIASED BIOINFORMATIC ANALYSIS OF MULTIPARAMETRIC FLOW CYTOMETRY
AU - Alexander Leonardo SILVA-JUNIOR
AU - Camilla Maria de Alencar SARAIVA
AU - Carla Roberta Peachazepi MORAES
AU - Bruno Kosa Lino DUARTE
AU - Gislaine Borba OLIVEIRA
AU - Katia Borgia Barbosa PAGNANO
AU - Herton Luiz Alves SALES FILHO
AU - Erich Vinicius DE PAULA
PY - 2026
DA - 2026/10/23
JO - Hematology, Transfusion and Cell Therapy
DO - 10.1016/j.htct.2026.107424
UR - https://doi.org/10.1016/j.htct.2026.107424
AB - Background: Acute Promyelocytic Leukemia (APL) is a subtype of acute myeloid leukemia with increased risk of acute hemorrhagic and thrombotic complications during the induction phase. The mechanisms by which hemostasis is activated in these patients is not completely understood. Aim: Here we investigated the association between the phenotype of myeloblasts assessed using an unbiased analytical approach with laboratory and clinical markers of disease severity in APL. Methods: Clinical and laboratory data from 36 patients newly diagnosed with APL were included in this cohort. Both peripheral blood (PB: n = 6) and bone marrow (BM; n = 30) samples, obtained at diagnosis, were used for flow cytometry (FC) analyzed using the following panels: i) ALOT: cyCD79a (PE), CD19 (PE-Cy-7), CD34 (PerCP-Cy5.5), CD3 (APC-H7), CD7 (APC), cyCD3 (V450) CD45 (V500) and cyMPO (FITC); ii) AML1: CD34 (PerCP-Cy5.5), CD13 (PE), CD45 (V500) and CD16 (FITC); iii) AML2: CD34 (PerCP-Cy5.5), CD14 (APC-H7), CD64 (PE), CD117 (PE-Cy7), CD45 (V500), HLA-DR (V450) and CD35 (FITC). In addition to classical FC analytical protocols, raw files were used in an unbiased bioinformatic analysis based on the individual expression profile of each cell, capable of identifying different expression signatures. Statistical analysis between groups was made with Mann-Whitney test and correlation with Spearman test, both considering a confidence interval of 95%. All analysis was performed in R Studio (v. 2026) using unsupflowhelper and flowCore packages. Results: Based on the expression signature derived from our unbiased analysis, the frequency of Myeloblast CD34high was higher in patients with CNS bleeding, whereas the frequency of mature hematopoietic cells and lymphocytes was associated with better survival. aPTT was positively correlated with Myeloblast CD34pos counts (rho = 0.48, p = 0.02), while no correlation was observed with prothrombin time, fibrinogen and platelet counts. Discussion and conclusion: Our unbiased analytical approach allows the identification of discrete populations that could be missed by conventional FC. Using this strategy, we were able to identify an association between Myeloblast CD34high and adverse outcomes, as well as between the presence of mature cells and more favorable prognosis during first induction. Reduction of mature B cells was associated with early mortality, while the association between aPTT with CD34pos myeloblasts suggests a role of these cells in coagulation activation, but additional studies are warranted to refine this hypothesis.
SN - 2531-1379
SN - 2531-1387
ER -