Precision Isolation of Circulating Leukemia Cells in Chronic Myelogenous Leukemia Patients Using a Novel Microfluidic Device and Its Clinical Applications

Author:

Ouyang Dongfang12ORCID,Ye Ningxin3,Yang Kun4,Wang Yiyang5,Hu Lina6,Chao Shuen12,Toner Mehmet12,Li Yonghua7

Affiliation:

1. Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Charlestown, Boston, MA 02129, USA

2. Shriners Hospital for Children, Boston, MA 02114, USA

3. Department of Biology, University of Ottawa, Ottawa, ON K1N 6N5, Canada

4. Department of Mechanical & Industrial Engineering, University of Toronto, Toronto, ON M5S 3E8, Canada

5. Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA

6. Department of Hematology, Shenzhen People’s Hospital, Shenzhen 518020, China

7. Department of Hematology, PLA General Hospital of Southern Theater Command, Guangzhou 510010, China

Abstract

Chronic Myelogenous Leukemia (CML) is a prevalent hematologic malignancy characterized by the malignant transformation of myeloid cells and their proliferation in the peripheral blood. The management of CML poses significant challenges, particularly in detecting and eradicating minimal residual disease, which is crucial for preventing relapse and improving survival outcomes. Traditional minimal residual disease detection methods, such as bone marrow aspiration, are invasive and have limitations which include the potential for sampling errors and false negatives. This study introduces a novel label-free microfluidic chip designed for the segregation and recovery of circulating leukemia cells, offering a non-invasive liquid biopsy approach with potential applications in precision medicine. Over July 2021 to October 2023, we recruited 56 CML patients across various disease stages and collected blood samples for analysis using our microfluidic device. The device demonstrated high efficacy in isolating circulating leukemia cells, with an optimal capture efficiency of 78% at a sample flow rate of 3 mL/h. Our results indicate that the microfluidic device can efficiently segregate and quantify circulating leukemia cells, providing a detailed understanding of CML progression and treatment response. The significant reduction in circulating leukemia cell counts in patients in complete remission highlights the device’s potential in monitoring treatment efficacy. Furthermore, the device’s sensitivity in detecting minimal residual disease could offer a more reliable prognostic tool for therapeutic decision-making in CML management.

Funder

National Institute of Health Grants

Science and Technology Project of Guangdong Province

Mitacs Elevate Fellowship

Publisher

MDPI AG

Subject

Cancer Research,Oncology

Reference37 articles.

1. (2023, October 30). Chronic Myeloid Leukemia—Cancer Stat Facts, Available online: https://seer.cancer.gov/statfacts/html/cmyl.html.

2. Allogeneic Hematopoietic Cell Transplantation: The State of the Art;Gyurkocza;Expert Rev. Hematol.,2014

3. Recent Advances in Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia;Bittencourt;Biol. Blood Marrow Transplant.,2020

4. The Progress of Small Molecule Targeting BCR-ABL in the Treatment of Chronic Myeloid Leukemia;Zhang;Mini Rev. Med. Chem.,2023

5. Monitoring of Minimal Residual Disease in Chronic Myeloid Leukemia;Faderl;Hematol. Oncol. Clin. N. Am.,2004

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