Tohoku J. Exp. Med., 2004, 203(3)

Detection of Clone-Specific Immunoglobulin Heavy Chain Genes in the Bone Marrow of B-cell-Lineage Lymphoma after Treatment

ATSUSHI HOSHINO, TADAO FUNATO, YASUHIKO MUNAKATA,¹ TOMONORI ISHII,¹ SHORI ABE,¹ KENICHI ISHIZAWA,¹ RYO ICHINOHASAMA,² JUNICHI KAMEOKA,¹ KUNIAKI MEGURO³ and TAKESHI SASAKI¹

Division of Molecular Diagnostics, ¹Rheumatology and Hematology, Department of Clinical Medicine, Tohoku University, School of Medicine,
²Department of Pathology, Tohoku University, School of Dental Medicine, Sendai 980-8574, and ³National Sendai Hospital, Sendai 983-8520

In order to determine the appropriate treatment of malignant lymphoma, it is important to know the degree to which extra-nodal invasion of lymphoma cells has occurred. We amplified complementarity-determining region (CDR) III genes in 64% of lymph node samples at the onset or relapse of B-cell-lineage non-Hodgkin’s lymphoma (NHL) in 22 patients. By using a clone-specific CDR III probe in each patient, we were able to detect minimal residual disease (MRD) of lymphoma cells in the bone marrow and/or blood in 9 out of 14 cases (64.2%) at the onset of the disease or relapse, whereas abnormal cells in the bone marrow and/or blood were identified by routine morphological analysis in only 4 out of 22 cases (18.2%). This indicates that extranodal invasion of malignant cells may be common in patients with NHL. In some cases, the clone-specific CDR III gene was still expressed in the samples of bone marrow and/or peripheral blood even after chemotherapy, when other markers associated with NHL were no longer expressed. Five out of six cases in this group had a worse outcome associated with NHL. On the other hand, most of the cases whose clone-specific CDR III gene was no longer expressed in the bone marrow and/or in circulation after treatment had a relatively fair prognosis. These results indicate that the detection at molecular level of MRD in extranodal organs may prove useful as a predictor of prognosis for NHL.

keywords —— non-Hodgkin’s lymphoma

© 2004 Tohoku University Medical Press

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Address for reprints: Tadao Funato, M.D., Ph.D., Division of Molecular Diagnostics, Tohoku University, School of Medicine, Seiryomachi 1-1, Aoba-ku, Sendai 980-8574, Japan.

e-mail: tfunato@mail.tains.tohoku.ac.jp

It is with regret that we report the sudden death of Dr. Atsushi Hoshino the first author, at the age of 44. We will all miss him.