Harmonization of molecular monitoring of chronic myeloid leukemia therapy in Japan
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Real-time quantitative polymerase chain reaction (RQ-PCR) has been widely used for molecular monitoring for patients with chronic myeloid leukemia (CML). Currently, RQ-PCR is not based on the concept of international scale (IS) in Japan; mainly because none of the domestic laboratories have obtained their own conversion factor (CF) which makes it possible to convert locally scaled BCR-ABL (BCR-ABL L) value to the IS (BCR-ABL IS). To join the global trend of molecular assessment of BCR-ABL in CML patients, we have tried to obtain a CF in Japan.
Samples from 55 patients were exchanged between the Japanese laboratory and the reference laboratory in Adelaide, and BCR-ABL and internal control gene transcripts of the samples were measured using RQ-PCR. The patient bias conversion method was used to determine the CF for the IS using the Bland and Altman method.
The local CF in the Japanese laboratory was determined to be 0.87. Based on this CF, 0.1% BCR-ABL IS, defined as major molecular response, becomes equivalent to 731 copy/μg RNA BCR-ABL L.
This study is the first to introduce a laboratory-specific CF for harmonizing RQ-PCR methodology for detecting BCR-ABL transcripts to Japan, which may open new windows for molecular assessment of CML patients in Japan.
KeywordsChronic myeloid leukemia BCR-ABL Real-time quantitative PCR International scale Conversion factor
This study was supported by the Epidemiological and Clinical Research Information Network (ECRIN). The following investigators in the Kanto CML study group participated in this study: Nobuyuki Aotsuka (Japanese Red Cross Soc., Narita Red Cross Hospital), Yokitaka Katsura (National Hospital Organization Mito Medical Center), Toshiko Motoji (Tokyo Women’s Medical University Hospital), Kentaro Yoshinaga (Tokyo Women’s Medical University Hospital), Masayuki Yamakura (Kameda General Hospital), Masami Takeuchi (Kameda General Hospital), Atsushi Wake (Toranomon Hospital), Hiroaki Tanaka (Oami Hospital), Naoshi Obara (University of Tsukuba), and Akihiro Nakajima (Tokyo Medical University Hachioji Medical Center).
Conflict of interest
Susan Branford received honoraria and research funding from Bristol Myers Squibb and Novartis. Chikashi Yoshida, Linda Fletcher, Kazuteru Ohashi, Hisashi Wakita, Takashi Kumagai, Masayuki Shiseki, Kousei Matsuei, Koiti Inokutchi, Yoshihiro Hatta, Yukari Shirasugi, Toshikazu Yamaguchi, Junichi Sakamoto, and Hisashi Sakamaki have no conflict of interest.
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