title: BCR-ABL1 transcript levels increase in peripheral blood but not in granulocytes after physical exercise in patients with chronic myeloid leukemia.
abstract: In chronic myeloid leukemia (CML) treatment response is determined by measurements of BCR-AB1L transcripts in peripheral blood by quantitative real-time PCR (qRT-PCR) and a 2-5 fold increase is considered a warning sign. The BCR-ABL1 gene is mainly expressed in myeloid cells whereas quantification of BCR-ABL1 is performed on the nucleated cell fraction of peripheral blood. Hence, leukocyte composition of the nucleated cell fraction may affect the result of BCR-ABL1 quantification. The aim of this study was to investigate if changes in leukocyte composition of peripheral blood had any effect on BCR-ABL1 transcript levels in CML patients. Six CML patients in complete cytogenetic remission (CCgR) performed a maximal physical exercise test. Blood samples were collected before exercise, at maximal exhaustion and after exercise. A biphasic increase in leukocyte count was observed and the relative proportion of granulocytes in peripheral blood changed significantly after exercise compared with baseline (p < 0.001). The BCR-ABL1 transcript level increased significantly following exercise, in nucleated cell fraction of peripheral blood (p < 0.05) but not in isolated granulocytes. In the nucleated cell fraction, the mean BCR-ABL1 transcript level was 3.3-fold (range 0.7-6.8) higher 180 min after exercise compared with baseline (p < 0.01). In conclusion, physical exercise induced significant increases in BCR-ABL1 transcript levels concomitant with changes in leukocyte content of peripheral blood. We therefore suggest that variations in leukocyte composition of peripheral blood, causing pre-analytic variations that affect BCR-ABL1 quantification, have to be accounted for. Consequently, small variations in BCR-ABL1 transcript levels should be interpreted cautiously in CML patients in CCgR.
authors.affiliation: Section of Hematology, Department of Internal Medicine, Sahlgrenska University Hospital, University of Gothenburg, Sweden. sofi a.jonsson@vgregion.se
authors.forename: Sofia
authors.initials: S
authors.lastname: Jönsson
authors.forename: Bob
authors.initials: B
authors.lastname: Olsson
authors.forename: Stefan
authors.initials: S
authors.lastname: Jacobsson
authors.forename: Lars
authors.initials: L
authors.lastname: Palmqvist
authors.forename: Anne
authors.initials: A
authors.lastname: Ricksten
authors.forename: Kerstin
authors.initials: K
authors.lastname: Ekeland-Sjöberg
authors.forename: Hans
authors.initials: H
authors.lastname: Wadenvik
mesh_terms: D000328:Adult; D000368:Aged; D015444:Exercise; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000097:blood* / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic; D006098:Granulocytes / Q000378:metabolism*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; C406060:abl-bcr fusion protein, human; D016044:Fusion Proteins, bcr-abl