Detection of minimal residual disease in patients with multiple myeloma using clonotype-specific PCR primers designed from DNA extracted from archival bone marrow slides
| Autor: | Naomi Shimizu, Toshihiro Miyamoto, Akira Yoshida, Saori Munemoto, Shinji Nakao, Noriko Kobayashi, Yoshiyasu Ogawa, Hiroyuki Takamatsu, Kazue Obata, Kinya Ohata, Toshihiro Fukushima, Ryoichi Murata, Toshiro Kurokawa, Tadashi Narisawa, Jun Ozaki, Nakayama Kouji, Yasushi Terasaki, Takanori Ueda, Yoshihisa Kumano, Go Aoki, Yukio Kondo, Takashi Yoshida |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Cancer Research Pathology medicine.medical_specialty Neoplasm Residual Genes Immunoglobulin Heavy Chain Immunoglobulins Polymerase Chain Reaction law.invention law Bone Marrow Predictive Value of Tests Genetics medicine Neoplasm Humans Molecular Biology Polymerase chain reaction Multiple myeloma Aged DNA Primers Retrospective Studies Histocytological Preparation Techniques biology Cell Biology Hematology Middle Aged medicine.disease Prognosis Minimal residual disease Transplantation medicine.anatomical_structure biology.protein Female Bone marrow Antibody Stem cell Multiple Myeloma |
| Zdroj: | Experimental hematology. 41(10) |
| ISSN: | 1873-2399 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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