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Complete detection of FR1 to FR3 primer-based PCR patterns of immunoglobulin heavy chain rearrangement in the BIOMED-2 protocol is associated with poor prognosis in patients with diffuse large B-cell lymphoma.
Yabushita, Tomohiro; Shimomura, Yoshimitsu; Maruoka, Hayato; Katoh, Daisuke; Yamashita, Daisuke; Satake, Hironaga; Hiramoto, Nobuhiro; Yoshioka, Satoshi; Yonetani, Noboru; Nishikori, Momoko; Morimoto, Takeshi; Imai, Yukihiro; Ishikawa, Takayuki.
Afiliación
  • Yabushita T; Department of Hematology Kobe City Medical Center General Hospital Kobe Japan.
  • Shimomura Y; International Research Center for Medical Sciences Kumamoto University Kumamoto Japan.
  • Maruoka H; Department of Hematology Kobe City Medical Center General Hospital Kobe Japan.
  • Katoh D; Department of Clinical Laboratory Kobe City Medical Center General Hospital Kobe Japan.
  • Yamashita D; Department of Hematology Kobe City Medical Center General Hospital Kobe Japan.
  • Satake H; Department of Pathology Kobe City Medical Center General Hospital Kobe Japan.
  • Hiramoto N; Department of Medical Oncology Kobe City Medical Center General Hospital Kobe Japan.
  • Yoshioka S; Department of Medical Oncology Kochi Medical School Kochi Japan.
  • Yonetani N; Department of Hematology Kobe City Medical Center General Hospital Kobe Japan.
  • Nishikori M; Department of Hematology Kobe City Medical Center General Hospital Kobe Japan.
  • Morimoto T; Department of Hematology Japanese Red Cross Osaka Hospital Osaka Japan.
  • Imai Y; Department of Hematology Kobe City Medical Center General Hospital Kobe Japan.
  • Ishikawa T; Department of Hematology and Oncology, Graduate School of Medicine Kyoto University Kyoto Japan.
EJHaem ; 5(4): 698-708, 2024 Aug.
Article en En | MEDLINE | ID: mdl-39157631
ABSTRACT
Somatic hypermutations (SHMs) in the variable region (VH) of the immunoglobulin heavy chain (IgH) gene are common in diffuse large B-cell lymphoma (DLBCL). Recently, IgH VH SHMs have become known as immunogenic neoantigens, but few studies have evaluated the prognostic impact of the frequency of VH SHMs in DLBCL. The BIOMED-2 protocol is the gold standard polymerase chain reaction (PCR) for clonality analysis in lymphoid malignancies, but can produce false negatives due to the presence of IgH VH SHMs. To overcome this problem, three primer sets were designed for the three framework regions (FR1, FR2, and FR3). We evaluated the predictive value of this PCR pattern in patients with DLBCL. To evaluate the prognostic impact of complete detection of the clonal amplifications (VHFR1-JH, VHFR2-JH, and VHFR3-JH) in the BIOMED-2 protocol, we retrospectively analyzed 301 DLBCL patients who were initially treated with anthracycline-based immunochemotherapy. Complete detection of the FR1 to FR3 primer-based IgH VH PCR patterns in the BIOMED-2 protocol was associated with low frequency of VH SHMs (p < 0.001). Patients who were positive for all these three PCRs (n = 79) were significantly associated with shorter 5-year overall survival (OS; 54.2% vs. 73.2%; p = 0.002) and progression-free survival (PFS; 34.3% vs. 59.3%; p < 0.001) compared to patients with other PCR patterns (n = 202). Specifically, the successful FR3-JH detection was associated with significantly worse OS (p < 0.001) and PFS (p < 0.001). PCR patterns of complete IgH rearrangement using the BIOMED-2 protocol are clinically meaningful indicators for prognostic stratification of DLBCL patients.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: EJHaem Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: EJHaem Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos