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Flow Cytometric Measurement of Blood Cells with BCR-ABL1 Fusion Protein in Chronic Myeloid Leukemia

Löf, Liza (author)
Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab
Arngården, Linda, 1984- (author)
Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab
Olsson-Strömberg, Ulla (author)
Uppsala universitet,Hematologi
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Siart, Benjamin (author)
Department of Anthropology, University of Vienna, Vienna, Austria
Jansson, Mattias (author)
Uppsala universitet,Medicinsk genetik och genomik,Science for Life Laboratory, SciLifeLab
Dahlin, Joakim S. (author)
Karolinska Institutet
Thörn, Ingrid, 1957- (author)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,Klinisk och experimentell patologi
Christiansson, Lisa, 1983- (author)
Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab
Hermansson, Monica (author)
Uppsala universitet,Medicinsk genetik och genomik,Science for Life Laboratory, SciLifeLab
Larsson, Anders (author)
Uppsala universitet,Biokemisk struktur och funktion
Ahlstrand, Erik, 1974- (author)
Dept. of Medicine, Division of Hematology, Örebro University Hospital, Örebro, Sweden
Wålinder, Göran (author)
Dept. of Medicine, Division of Hematology, Örebro University Hospital, Örebro, Sweden
Söderberg, Ola, 1966- (author)
Uppsala universitet,Institutionen för farmaceutisk biovetenskap
Rosenquist, Richard (author)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,Experimentell och klinisk onkologi
Landegren, Ulf (author)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylära verktyg
Kamali-Moghaddam, Masood (author)
Uppsala universitet,Molekylära verktyg,Science for Life Laboratory, SciLifeLab
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 (creator_code:org_t)
2017-04-04
2017
English.
In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7:1
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Chronic myeloid leukemia (CML) is characterized in the majority of cases by a t(9;22)(q34;q11) translocation, also called the Philadelphia chromosome, giving rise to the BCR-ABL1 fusion protein. Current treatment with tyrosine kinase inhibitors is directed against the constitutively active ABL1 domain of the fusion protein, and minimal residual disease (MRD) after therapy is monitored by real-time quantitative PCR (RQ-PCR) of the fusion transcript. Here, we describe a novel approach to detect and enumerate cells positive for the BCR-ABL1 fusion protein by combining the in situ proximity ligation assay with flow cytometry as readout (PLA-flow). By targeting of the BCR and ABL1 parts of the fusion protein with one antibody each, and creating strong fluorescent signals through rolling circle amplification, PLA-flow allowed sensitive detection of cells positive for the BCR-ABL1 fusion at frequencies as low as one in 10,000. Importantly, the flow cytometric results correlated strongly to those of RQ-PCR, both in diagnostic testing and for MRD measurements over time. In summary, we believe this flow cytometry-based method can serve as an attractive approach for routine measurement of cells harboring BCR-ABL1 fusions, also allowing simultaneously assessment of other cell surface markers as well as sensitive longitudinal follow-up.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Hematologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Hematology (hsv//eng)

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