Development and evaluation of a rapid one-step high sensitivity real-time quantitative PCR system for minor BCR-ABL (e1a2) test in Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL)

Michihiro Hidaka; Koiti Inokuchi; Nobuhiko Uoshima; Naoto Takahashi; Nao Yoshida; Shuichi Ota; Hirohisa Nakamae; Hiromi Iwasaki; Kenichiro Watanabe; Yoshiyuki Kosaka; Norio Komatsu; Kuniaki Meguro; Yuho Najima; Tetsuya Eto; Takeshi Kondo; Shinya Kimura; Chikashi Yoshida; Yuichi Ishikawa; Masashi Sawa; Tomoko Hata; Keizo Horibe; Hiroatsu Iida; Takeshi Shimomura; Nobuaki Dobashi; Isamu Sugiura; Junya Makiyama; Naoyuki Miyagawa; Asuka Sato; Ryuta Ito; Itaru Matsumura; Yuzuru Kanakura; Tomoki Naoe

doi:10.1093/jjco/hyad156

Development and evaluation of a rapid one-step high sensitivity real-time quantitative PCR system for minor BCR-ABL (e1a2) test in Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL)

Jpn J Clin Oncol. 2024 Feb 7;54(2):153-159. doi: 10.1093/jjco/hyad156.

Authors

Michihiro Hidaka¹, Koiti Inokuchi², Nobuhiko Uoshima³, Naoto Takahashi⁴, Nao Yoshida⁵, Shuichi Ota⁶, Hirohisa Nakamae⁷, Hiromi Iwasaki⁸, Kenichiro Watanabe⁹, Yoshiyuki Kosaka¹⁰, Norio Komatsu¹¹, Kuniaki Meguro¹², Yuho Najima¹³, Tetsuya Eto¹⁴, Takeshi Kondo¹⁵, Shinya Kimura¹⁶, Chikashi Yoshida¹⁷, Yuichi Ishikawa¹⁸, Masashi Sawa¹⁹, Tomoko Hata²⁰, Keizo Horibe²¹, Hiroatsu Iida²², Takeshi Shimomura²³, Nobuaki Dobashi²⁴, Isamu Sugiura²⁵, Junya Makiyama²⁶, Naoyuki Miyagawa²⁷, Asuka Sato²⁸, Ryuta Ito²⁸, Itaru Matsumura²⁹, Yuzuru Kanakura³⁰, Tomoki Naoe³¹

Affiliations

¹ Department of Hematology, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan.
² Department of Hematology, Nippon Medical School, Tokyo, Japan.
³ Department of Hematology, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan.
⁴ Department of Hematology, Nephrology and Rheumatology, Akita University Graduate School of Medicine, Akita, Japan.
⁵ Department of Hematology and Oncology, Children's Medical Center, Japanese Red Cross Aichi Medical Center Nagoya First Hospital, Aichi, Japan.
⁶ Department of Hematology, Sapporo Hokuyu Hospital, Hokkaido, Japan.
⁷ Department of Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
⁸ Department of Hematology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.
⁹ Department of Hematology and Oncology, Shizuoka Children's Hospital, Shizuoka, Japan.
¹⁰ Department of Hematology and Oncology, Center of Childhood Cancer, Hyogo Prefectural Kobe Children's Hospital, Hyogo, Japan.
¹¹ Department of Hematology, Juntendo University School of Medicine, Tokyo, Japan.
¹² Department of Hematology, National Hospital Organization Sendai Medical Center, Miyagi, Japan.
¹³ Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
¹⁴ Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan.
¹⁵ Blood Disorders Center, Aiiku Hospital, Hokkaido, Japan.
¹⁶ Department of Hematology, Respiratory Medicine and Oncology, Saga University, Saga, Japan.
¹⁷ Department of Hematology, National Hospital Organization Mito Medical Center, Ibaraki, Japan.
¹⁸ Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Aichi, Japan.
¹⁹ Department of Hematology and Oncology, Anjo Kosei Hospital, Aichi, Japan.
²⁰ Department of Hematology, Nagasaki University Hospital, Nagasaki, Japan.
²¹ Department of Pediatrics, National Hospital Organization Nagoya Medical Center, Aichi, Japan.
²² Department of Hematology, National Hospital Organization Nagoya Medical Center, Aichi, Japan.
²³ Department of Hematology, National Hospital Organization Hiroshimanishi Medical Center, Hiroshima, Japan.
²⁴ Department of Clinical Oncology and Hematology, The Jikei University Daisan Hospital, Tokyo, Japan.
²⁵ Department of Hematology and Oncology, Toyohashi Municipal Hospital, Aichi, Japan.
²⁶ Department of Hematology/Oncology, Institute of Medical Science, The University of Tokyo Hospital, Tokyo, Japan.
²⁷ Division of Hematology/Oncology, Kanagawa Children's Medical Center, Kanagawa, Japan.
²⁸ Diagnostic Division, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan.
²⁹ Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osaka, Japan.
³⁰ Sumitomo Hospital, Osaka, Japan.
³¹ National Hospital Organization Nagoya Medical Center, Aichi, Japan.

Abstract

Objective: Minimal residual disease assessment of BCR-ABL messenger ribonucleic acid levels is crucial in Philadelphia chromosome-positive acute lymphoblastic leukemia for prognosis and treatment planning. However, accurately quantifying minor BCR-ABL transcripts, which comprise 70% of Philadelphia chromosome-positive acute lymphoblastic leukemia cases, lacks a national-approved method.

Methods: We developed the "Otsuka" minor BCR-ABLmessenger ribonucleic acid assay kit with exceptional precision (0.00151%). Minor BCR-ABL messenger ribonucleic acid levels were analyzed in 175 adults, 36 children with acute lymphoblastic leukemia and 25 healthy individuals to evaluate the kit's performance.

Results: The "Otsuka" kit showed high concordance with a commonly used chimeric gene screening method, indicating reliable detection of positive cases. Quantitative results demonstrated a robust correlation with both a laboratory-developed test and a diagnostic research product. The "Otsuka" kit performs comparably or even surpass to conventional products, providing valuable insights into Philadelphia chromosome-positive acute lymphoblastic leukemia pathology.

Conclusions: The 'Otsuka" minor BCR-ABL messenger ribonucleic acid assay kit exhibits excellent performance in quantifying minor BCR-ABL transcripts in Philadelphia chromosome-positive acute lymphoblastic leukemia patients. Our results align well with established screening methods and show a strong correlation with laboratory-developed tests and diagnostic research products. The "Otsuka" kit holds great promise as a valuable tool for understanding Philadelphia chromosome-positive acute lymphoblastic leukemia pathology and guiding effective treatment strategies.

Keywords: Philadelphia-positive acute lymphoblastic leukemia; minimal residual disease; minor BCR-ABL.

MeSH terms

Adult
Child
Fusion Proteins, bcr-abl / analysis
Fusion Proteins, bcr-abl / genetics
Humans
Philadelphia Chromosome*
Precursor Cell Lymphoblastic Leukemia-Lymphoma* / genetics
RNA
Real-Time Polymerase Chain Reaction

Substances

Fusion Proteins, bcr-abl
RNA

Grants and funding

Otsuka Pharmaceutical Co., Ltd.