间期荧光原位杂交检测到的染色体异常在初诊多发性骨髓瘤患者中的临床意义。

Clinical significance of chromosomal abnormalities detected by interphase fluorescence in situ hybridization in newly diagnosed multiple myeloma patients.

机构信息

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.

出版信息

Chin Med J (Engl). 2011 Oct;124(19):2981-5.

PMID:22040539

Abstract

BACKGROUND

Chromosome 13q14 deletion (del13q14), chromosome 1q21 gain (amp1q21) and chromosome 17p13 deletion (del17p13) are the most frequent chromosomal aberrations in multiple myeloma (MM). They play an important role in prognosis. The aim of this study was to investigate the clinical significance of the chromosomal changes in Chinese MM patients.

METHODS

Interphase fluorescence in situ hybridization (FISH) on bone marrow (BM) cells was performed in 72 enrolled MM patients. Relationships between chromosomal abnormalities and clinical features, response to therapies and prognosis were analyzed.

RESULTS

As a result of interphase FISH, 77.8% (56/72) patients had chromosome changes. The incidences of each probe were RB1 51.4% (37/72), D13S319 47.2% (34/72), 1q21 45.8% (33/72) and p53 22.2% (12/72). Osteolytic lesion, BM plasma cells index, serum calcium and serum M component were significantly correlated to del13q14. BM plasma cells and hemoglobin were correlated to amp1q21. Serum lactate dehydrogenase (LDH) was correlated with del17p13. Patients with del13q14 treated with bortezomib had a notably higher overall response rate than the patients treated with traditional chemotherapies (93% vs. 65%, P = 0.048). Patients carrying amp1q21 or/and del17p13 did not achieve satisfactory response to bortezomib. The median progression-free survival (PFS) for patients with amp1q21 was 5 months and patients without amp1q21 got 9-month PFS (P = 0.001). The median PFS for patients with del13q14 was 5 months (vs. 8 months, P = 0.026). The median PFS for patients with del17p13 was 3 months (vs. 8 months, P = 0.002). Patients with β(2)-microglobulin > 5.5 mg/L also had a worse outcome, whose median PFS was 5 months (vs. 8 months, P = 0.016).

CONCLUSIONS

The prevalence of chromosomal abnormalities of MM patients was similar in Chinese and Caucasian people. Genetic changes were associated with patients' responses to therapies and prognosis.

摘要

背景

13q14 染色体缺失（del13q14）、1q21 染色体增益（amp1q21）和 17p13 染色体缺失（del17p13）是多发性骨髓瘤（MM）中最常见的染色体异常。它们在预后中起着重要作用。本研究旨在探讨中国 MM 患者染色体改变的临床意义。

方法

对 72 例 MM 患者的骨髓（BM）细胞进行间期荧光原位杂交（FISH）。分析染色体异常与临床特征、对治疗的反应和预后的关系。

结果

通过间期 FISH，77.8%（56/72）的患者存在染色体改变。每个探针的发生率分别为 RB1 51.4%（37/72）、D13S319 47.2%（34/72）、1q21 45.8%（33/72）和 p53 22.2%（12/72）。溶骨性病变、BM 浆细胞指数、血清钙和血清 M 成分与 del13q14 显著相关。BM 浆细胞和血红蛋白与 amp1q21 相关。血清乳酸脱氢酶（LDH）与 del17p13 相关。接受硼替佐米治疗的 del13q14 患者总缓解率明显高于接受传统化疗的患者（93% vs. 65%，P=0.048）。携带 amp1q21 或/和 del17p13 的患者对硼替佐米反应不佳。携带 amp1q21 的患者中位无进展生存期（PFS）为 5 个月，无 amp1q21 的患者中位 PFS 为 9 个月（P=0.001）。del13q14 患者的中位 PFS 为 5 个月（vs. 8 个月，P=0.026）。del17p13 患者的中位 PFS 为 3 个月（vs. 8 个月，P=0.002）。β（2）-微球蛋白>5.5mg/L 的患者预后较差，中位 PFS 为 5 个月（vs. 8 个月，P=0.016）。