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.

Key Words::

• Chronic myeloid leukemia
• imatinib
• BCR-ABL
• complete cytogenetic remission
• reverse transcriptase polymerase chain reaction
• exercise

Acknowledgments

This work was supported by grants from the Swedish Research Council (529-2004-6512; 521-2006-5103), The Swedish federal government under the LUA/ALF agreement, the Sahlgrenska University Hospital Foundation, the Foundations of the National Board of Health and Welfare, the Åke Wiberg Foundation, the Jeansson Foundations, the Tore Nilsson Foundation for Medical Research, the Magnus Bergvall Foundation, the Wilhelm and Martina Lundgren Science Foundation. The expert technical assistance provided by Irene Andersson was much appreciated.

Declaration of interest: The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.