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Article

The Impact of Targeted Therapies on Red Blood Cell Aggregation in Patients with Chronic Lymphocytic Leukemia Evaluated Using Software Image Flow Analysis

by
Anika Alexandrova-Watanabe
1,2,†,
Emilia Abadjieva
1,2,†,
Lidia Gartcheva
3,
Ariana Langari
2,4,
Miroslava Ivanova
4,
Margarita Guenova
3,
Tihomir Tiankov
1,2,
Velichka Strijkova
5,
Sashka Krumova
4 and
Svetla Todinova
2,4,*
1
Institute of Mechanics, Bulgarian Academy of Sciences, “Acad. G. Bontchev” Str. 4, 1113 Sofia, Bulgaria
2
Center of Competence at Mechatronics and Clean Technologies—MIRACle, “Acad. G. Bontchev” Str. 4, 1113 Sofia, Bulgaria
3
National Specialized Hospital for Active Treating of Hematological Diseases, Zdrave Str. 2, 1756 Sofia, Bulgaria
4
Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, “Acad. G. Bontchev” Str. 21, 1113 Sofia, Bulgaria
5
Institute of Optical Materials and Technologies “Acad. Yordan Malinovski”, Bulgarian Academy of Sciences, “Acad. G. Bontchev” Str. 109, 1113 Sofia, Bulgaria
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Micromachines 2025, 16(1), 95; https://doi.org/10.3390/mi16010095
Submission received: 2 December 2024 / Revised: 8 January 2025 / Accepted: 10 January 2025 / Published: 15 January 2025

Abstract

Chronic lymphocytic leukemia (CLL), the most common type of leukemia, remains incurable with conventional therapy. Despite advances in therapies targeting Bruton’s tyrosine kinase and anti-apoptotic protein BCL-2, little is known about their effect on red blood cell (RBC) aggregation in blood flow. In this study, we applied a microfluidic device and a newly developed Software Image Flow Analysis to assess the extent of RBC aggregation in CLL patients and to elucidate the hemorheological effects of the commonly applied therapeutics Obinutuzumab/Venetoclax and Ibrutinib. The results revealed that, in RBC samples from untreated CLL patients, complex 3D clusters of large RBC aggregates are formed, and their number is significantly increased compared to healthy control samples. The application of the Obinutuzumab/Venetoclax combination did not affect this aspect of RBCs’ rheological behavior. In contrast, targeted therapy with Ibrutinib preserves the aggregation state of CLL RBCs to levels seen in healthy controls, demonstrating that Ibrutinib mitigates the alterations in the rheological properties of RBCs associated with CLL. Our findings highlight the alterations in RBC aggregation in CLL and the impact of different targeted therapies on RBCs’ rheological properties, which is critical for predicting the potential complications and side effects of CLL treatments, particularly concerning blood flow dynamics.
Keywords: chronic lymphocytic leukemia; red blood cell aggregation; microfluidic device; software image flow analysis; red blood cell morphology; Obinutuzumab; Venetoclax; Ibrutinib chronic lymphocytic leukemia; red blood cell aggregation; microfluidic device; software image flow analysis; red blood cell morphology; Obinutuzumab; Venetoclax; Ibrutinib

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MDPI and ACS Style

Alexandrova-Watanabe, A.; Abadjieva, E.; Gartcheva, L.; Langari, A.; Ivanova, M.; Guenova, M.; Tiankov, T.; Strijkova, V.; Krumova, S.; Todinova, S. The Impact of Targeted Therapies on Red Blood Cell Aggregation in Patients with Chronic Lymphocytic Leukemia Evaluated Using Software Image Flow Analysis. Micromachines 2025, 16, 95. https://doi.org/10.3390/mi16010095

AMA Style

Alexandrova-Watanabe A, Abadjieva E, Gartcheva L, Langari A, Ivanova M, Guenova M, Tiankov T, Strijkova V, Krumova S, Todinova S. The Impact of Targeted Therapies on Red Blood Cell Aggregation in Patients with Chronic Lymphocytic Leukemia Evaluated Using Software Image Flow Analysis. Micromachines. 2025; 16(1):95. https://doi.org/10.3390/mi16010095

Chicago/Turabian Style

Alexandrova-Watanabe, Anika, Emilia Abadjieva, Lidia Gartcheva, Ariana Langari, Miroslava Ivanova, Margarita Guenova, Tihomir Tiankov, Velichka Strijkova, Sashka Krumova, and Svetla Todinova. 2025. "The Impact of Targeted Therapies on Red Blood Cell Aggregation in Patients with Chronic Lymphocytic Leukemia Evaluated Using Software Image Flow Analysis" Micromachines 16, no. 1: 95. https://doi.org/10.3390/mi16010095

APA Style

Alexandrova-Watanabe, A., Abadjieva, E., Gartcheva, L., Langari, A., Ivanova, M., Guenova, M., Tiankov, T., Strijkova, V., Krumova, S., & Todinova, S. (2025). The Impact of Targeted Therapies on Red Blood Cell Aggregation in Patients with Chronic Lymphocytic Leukemia Evaluated Using Software Image Flow Analysis. Micromachines, 16(1), 95. https://doi.org/10.3390/mi16010095

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