Detection of minimal residual disease in patients with multiple myeloma using clonotype-specific PCR primers designed from DNA extracted from archival bone marrow slides

Hiroyuki Takamatsu, Yoshiyasu Ogawa, Noriko Kobayashi, Kazue Obata, Tadashi Narisawa, Kouji Nakayama, Saori Munemoto, Go Aoki, Kinya Ohata, Yoshihisa Kumano, Jun Ozaki, Ryoichi Murata, Yukio Kondo, Yasushi Terasaki, Toshiro Kurokawa, Toshihiro Miyamoto, Naomi Shimizu, Toshihiro Fukushima, Akira Yoshida, Takanori UedaTakashi Yoshida, Shinji Nakao

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5 Citations (Scopus)

Abstract

Polymerase chain reaction (PCR)-negative molecular complete remission (mCR) can be induced by stem cell transplantation in some patients with multiple myeloma (MM) and is associated with long-term progression-free survival (PFS). The detection of molecular minimal residual disease (MRD), however, requires fresh or frozen materials for designing clone-specific primers, which are not always readily available. In this study, we used DNA extracted from archival bone marrow (BM) slides for PCR to detect MRD in 50 patients with MM who received various induction therapies and autologous peripheral blood stem cell transplantation (ASCT). Clonotype-specific immunoglobulin (Ig) H PCR primers were prepared for 32 of 50 cases (64%) using BM slides, and for 9 of 14 cases (64%) using fresh BM cells. DNA in peripheral blood stem cell autografts of the 22 patients who achieved at least a partial response after ASCT was subjected to PCR to amplify clonotype-specific rearranged IgH gene sequences. The median PFS of the eight patients with MRD-positive autografts was 18 months, whereas that of 14 patients with MRD-negative autografts was not reached at a median follow-up of 27 months (p = 0.012). Post-ASCT PFS of the four patients who achieved mCR was 100% at a median follow-up of 47 months. These results indicate that archival BM slides can serve as a source of DNA for preparing clonotype-specific primers for MRD monitoring in patients with MM whose cryopreserved myeloma cells are not available for DNA preparation. Our results also suggest that patients with MM who received MRD-negative autografts and achieved mCR have a long PFS.

Original languageEnglish
Pages (from-to)894-902
Number of pages9
JournalExperimental Hematology
Volume41
Issue number10
DOIs
Publication statusPublished - Oct 2013

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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    Takamatsu, H., Ogawa, Y., Kobayashi, N., Obata, K., Narisawa, T., Nakayama, K., Munemoto, S., Aoki, G., Ohata, K., Kumano, Y., Ozaki, J., Murata, R., Kondo, Y., Terasaki, Y., Kurokawa, T., Miyamoto, T., Shimizu, N., Fukushima, T., Yoshida, A., ... Nakao, S. (2013). Detection of minimal residual disease in patients with multiple myeloma using clonotype-specific PCR primers designed from DNA extracted from archival bone marrow slides. Experimental Hematology, 41(10), 894-902. https://doi.org/10.1016/j.exphem.2013.05.004