B세포비호지킨림프종 환자의 골수에서 면역글로불린유전자재배열 검사의 임상적 의의
Clinical Significance of Clonal Rearrangement of the Immunoglobulin Gene in the Bone Marrow of Patients with B-cell Non-Hodgkin Lymphoma
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
배경: 초기 비호지킨림프종(Non-Hodgkin lymphoma, NHL)에서 진단 시 형태학적 관찰을 통해 골수의 미세한 변화를 인지하기 어렵다. 특히 골수생검의 질이 부적합할 경우 골수흡인의 현미경학적 소견에 따라 비호지킨림프종 골수침범 여부 판단이 제한적으로 이루어질 수밖에 없다. 본 연구에서는 병기 결정을 위해서 골수 검사를 시행한 B세포비호지킨림프종 환자를 대상으로 골수의 형태학적 소견과 면역글로불린유전자재배열 검사 결과를 비교하고 병기 결정에 있어 클론성 면역글로불린유전자재배열검사의 유용성을 평가하고자 하였다. 방법: 42명의 B세포비호지킨림프종 환자를 대상으로 하였다. IdentiCloneTM Clonality assay (InVivoScribe Technologies, USA)를 이용하여 면역글로불린 중쇄(IGH), 면역글로불린 κ (IGK) 및 λ (IGL) 경쇄 유전자의 클론성 재배열을 확인하였다. 면역글로불린유전자재배열의 단클론성 유무에 따른 환자의 임상적 특성과 치료 반응을 비교하였다. 결과: 42명의 환자 중 9명의 환자(21.4%)에서 단클론면역글로불린 유전자재배열이 관찰되었다. 형태학적 골수침범은 2명의 환자(4.8%)에서만 관찰되었다. 골수검체에서 단클론면역글로불린유전자재배열 양성률은 임상적 병기 및 international prognostic index (P<0.01)와 유의한 상관성을 보였다. 단클론면역글로불린유전자재배열이 있는 환자는 단클론성이 관찰되지 않는 환자에 비해 유의하게 재발률이 높았으며(P=0.014), 2년간 전체 생존율도 낮았다(P<0.01). 결론: 클론성 면역글로불린유전자재배열 검사는 형태학적으로 정상 골수소견을 보이는 환자에서 유의하게 낮은 전체 생존율과 관련된 잠재적인 비호지킨림프종의 골수침범 여부를 확인하는 데 기여할 수 있을 것이다.
Abstract
Background: In the early stages of non-Hodgkin lymphoma (NHL), it can be difficult to recognize minimal morphological changes in the bone marrow (BM). In particular, when the quality of the BM biopsy is poor, determining BM involvement is limited to microscopic findings on BM aspiration. In this study, we compared the results of clonal immunoglobulin (IG) gene rearrangements with BM morphology results in B-cell NHL patients who underwent BM analysis as a staging workup and evaluated the usefulness of the clonal IG gene rearrangements for staging. Methods: Forty two B-cell NHL patients were analyzed. Clonal rearrangements of the IG heavy chain (IGH), κ light chain (IGK) and λ light chain (IGL) genes were detected using the IdentiCloneTM Clonality assay (InVivoScribe Technologies, USA). Clinical characteristics and outcomes were evaluated based on the detection of monoclonal IG gene rearrangements. Results: Monoclonal IG gene rearrangements were found in 9 of 42 patients (21.4%). Microscopic BM involvement was found in only 2 of 42 patients (4.8%). The monoclonality rate of IG genes in BM was correlated with clinical stage and the international prognostic index (P<0.01). Patients with monoclonal IG gene rearrangements in BM had a significantly higher relapse rate (P=0.014) and poorer overall survival at 2 yr (P<0.01). Conclusions: Clonality analysis of BM in B-cell NHL can contribute to identification of patients with occult BM involvement with a significantly poorer overall survival despite normal BM histology.
참고문헌 (15)
- Swerdlow SH, "WHO Classification of tumours of haematopoietic and lymphoid tissues" (2008), IARC Press
- van Dongen JJ, "Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations : report of the BIOMED-2 Concerted Action BMH4-CT98-3936", Leukemia, 17, pp.2257~2317 (2003)
- Mitterbauer-Hohendanner G, "Prognostic significance of molecular staging by PCR-amplification of immunoglobulin gene rearrangements in diffuse large B-cell lymphoma(DLBCL)", Leukemia, 18, pp.1102~1107 (2004)
- Chute DJ, "Detection of immunoglobulin heavy chain gene rearrangements in classic hodgkin lymphoma using commercially available BIOMED-2 primers", Diagn Mol Pathol, 17, pp.65~72 (2008)
- "A predictive model for aggressive non-Hodgkin’s lymphoma. The International Non-Hodgkin’s Lymphoma Prognostic Factors Project", N Engl J Med, 329, pp.987~994 (1993)
- Cheson BD, "Revised response criteria for malignant lymphoma", J Clin Oncol, 25, pp.579~586 (2007)
- 오혜룡, "카파 및 람다 면역글로불린 경쇄 유전자의 클론성 재배열을 동시에 보이는 람다 경쇄 표현 폐 MALT 림프종 1예", Annals of Laboratory Medicine, 29(3), pp.256~261 (2009), 대한진단검사의학회
- Langerak AW, "Polymerase chain reaction-based clonality testing in tissue samples with reactive lymphoproliferations: usefulness and pitfalls. A report of the BIOMED-2 Concerted Action BMH4-CT98-3936", Leukemia, 21, pp.222~229 (2007)
- Macintyre E, "Non-Hodgkin’s Lymphoma : Molecular Features of B Cell Lymphoma", Hematology Am Soc Hematol Educ Program, 2000(1), pp.180~204 (2000)
- Zwicky CS, "Eradication of polymerase chain reaction detectable immunoglobulin gene rearrangement in non-Hodgkin’s lymphoma is associated with decreased relapse after autologous bone marrow transplantation", Blood, 88, pp.3314~3322 (1996)
- Langerak AW, "EuroClonality", BIOMED-2 guidelines for interpretation and reporting of Ig, Leukemia, pp.2012, 26[DOI]
- Halldorsdottir AM, "Application of BIOMED-2 clonality assays to formalin-fixed paraffin embedded follicular lymphoma specimens : superior performance of the IGK assays compared to IGH for suboptimal specimens", Leuk Lymphoma, 48, pp.1338~1343 (2007)
- Payne K, "BIOMED-2 PCR assays for IGK gene rearrangements are essential for B-cell clonality analysis in follicular lymphoma", Br J Haematol, 155, pp.84~92 (2011)
- van Krieken JH, "Improved reliability of lymphoma diagnostics via PCR-based clonality testing : report of the BIOMED-2 Concerted Action BHM4-CT98-3936", Leukemia, 21, pp.201~206 (2007)
- 성지연, "면역글로불린 유전자 재배열 분석법: BIOMED-2와 통상적 Nested PCR법의 비교", Laboratory Medicine Online, 1(4), pp.195~201 (2011), 대한진단검사의학회