153例多发性骨髓瘤的细胞遗传学分析

doi:10.3969/j.issn.1673-8640.2020.12.009

摘要/Abstract

摘要：

目的评价细胞遗传学分析在多发性骨髓瘤（MM）中的应用价值。方法采用核型分析和间期荧光原位杂交（iFISH）对153例MM的细胞遗传学结果进行回顾性分析。结果 MM患者染色体异常主要集中在13、9、14、1、8号染色体上;核型分析联合iFISH染色体异常检出率可达79.1%,多数为复杂的染色体异常,其中9例染色体核型异常,但iFISH阴性;在这9例中,有7例患者的无疾病进展时间（PFS）<3年,其中2例患者死于感染和心力衰竭。结论常规染色体核型分析能提供完整的细胞遗传学资料,虽然检出率偏低,但是在科学研究和临床应用中仍不可或缺。

关键词: 多发性骨髓瘤, 细胞遗传学, 染色体核型

Abstract:

Objective To evaluate the role of cytogenetic analysis in multiple myeloma（MM）. Methods The cytogenetic analysis in 153 newly-diagnosed cases of MM was performed retrospectively. Results The recurrent chromosomal abnormality were most concentrated on the chromosome 13,9,14,1 and 8. The combination of conventional cytogenetics and iFISH displayed genetic abnormalities up to 79.1% and showed the majority of cases had complex chromosome karyotypes. There were 9 cases of abnormal karyotypes by conventional cytogenetics,but with negative-iFISH results. The 7 of 9 cases were with progression-free survival（PFS） less than 3 years,including 2 cases of death from infection and heart failure. Conclusions Even with low efficiency,conventional cytogenetics is still an essential application for offering full cytogenetic profile,and it is still indispensable for current scientific research and clinical practice.

Key words: Multiple myeloma, Cytogenetics, Karyotype

中图分类号:

R446.1

徐凯红, 牧启田, 欧阳桂芳, 严笑. 153例多发性骨髓瘤的细胞遗传学分析[J]. 检验医学, 2020, 35(12): 1243-1247.

XU Kaihong, MU Qitian, OUYANG Guifang, YAN Xiao. Cytogenetic analysis of 153 newly-diagnosed cases of multiple myeloma[J]. Laboratory Medicine, 2020, 35(12): 1243-1247.

图/表 6

参考文献 19

[1]	LIWING J,UTTERVALL K,LUND J,et al.Improved survival in myeloma patients:starting to close in on the gap between elderly patients and a matched normal population[J]. Br J Haematol,2014,164(5):684-693.
[2]	ABDALLAH N,RAJKUMAR S V,GREIPP P,et al.Cytogenetic abnormalities in multiple myeloma:association with disease characteristics and treatment response[J]. Blood Cancer J,2020,10(8):82-87.
[3]	SONNEVELD P,AVET-LOISEAU H,LONIAL S,et al.Treatment of multiple myeloma with high-risk cytogenetics:a consensus of the International Myeloma Working Group[J]. Blood,2016,127(24):2955-2962.
[4]	AGNELLI L,TASSONE P,NERI A.Molecular profiling of multiple myeloma:from gene expression analysis to next-generation sequencing[J]. Expert Opin Biol Ther,2013,13(Suppl 1):S55-S68.
[5]	RACK K,VIDREQUIN S,DARGENT J L.Genomic profiling of myeloma:the best approach,a comparison of cytogenetics,FISH and array-CGH of 112 myeloma cases[J]. J Clin Pathol,2016,69(1):82-86.
[6]	MCGOWAN-JORDAN J,SIMONS A,SCHMID M.An international system for human cytogenomic nomenclature[M]. Switzerland: S Karger AG,2016.
[7]	VAN WIER S,BRAGGIO E,BAKER A,et al.Hypodiploid multiple myeloma is characterized by more aggressive molecular markers than non-hyperdiploid multiple myeloma[J]. Haematologica,2013,98(10):1586-1592.
[8]	ZANDECKI M,LAÏ J L,FACON T.Multiple myeloma:almost all patients are cytogenetically abnormal[J]. Br J Haematol,1996,94(2):217-227.
[9]	RADOCHA J,MAISNAR V,POUR L,et al.Validation of multiple myeloma risk stratification indices in routine clinical practice:analysis of data from the Czech Myeloma Group Registry of Monoclonal Gammopathies[J]. Cancer Med,2018,7(8):4132-4145.
[10]	LU J,LU J,CHEN W,et al.Clinical features and treatment outcome in newly diagnosed Chinese patients with multiple myeloma:results of a multicenter analysis[J]. Blood Cancer J,2014,4(8):e239.
[11]	BYUN J M,SHIN D Y,HONG J,et al.Distinct predictive impact of FISH abnormality in proteasome inhibitors and immunomodulatory agents response:redefining high-risk multiple myeloma in Asian patients[J]. Cancer Med,2018,7(3):831-841.
[12]	MIKULASOVA A,SMETANA J,WAYHELOVA M,et al.Genomewide profiling of copy-number alteration in monoclonal gammopathy of undetermined significance[J]. Eur J Haematol,2016,97(6):568-575.
[13]	MOHAMED A N,BENTLEY G,BONNETT M L,et al.Chromosome aberrations in a series of 120 multiple myeloma cases with abnormal karyotypes[J]. Am J Hematol,2007,82(12):1080-1087.
[14]	MERZ M,JAUCH A,HIELSCHER T,et al.Prognostic significance of cytogenetic heterogeneity in patients with newly diagnosed multiple myeloma[J]. Blood Adv,2017,2(1):1-9.
[15]	KUMAR S,FONSECA R,KETTERLING R P,et al.Trisomies in multiple myeloma:impact on survival in patients with high-risk cytogenetics[J]. Blood,2012,119(9):2100-2105.
[16]	CHRETIEN M L,CORRE J,LAUWERS-CANCES V,et al.Understanding the role of hyperdiploidy in myeloma prognosis:which trisomies really matter?[J]. Blood,2015,126(25):2713-2719.
[17]	CARBALLO-ZARATE A A,MEDEIROS L J,FANG L,et al. Additional-structural-chromosomal aberrations are associated with inferior clinical outcome in patients with hyperdiploid multiple myeloma:a single-institution experience[J]. Mod Pathol,2017,30(6):843-853.
[18]	DURU A D,SUTLU T,WALLBLOM A,et al.Deletion of chromosomal region 8p21 confers resistance to bortezomib and is associated with upregulated decoy TRAIL receptor expression in patients with multiple myeloma[J]. PLoS One,2015,10(9):e0138248.
[19]	GLITZA I C,LU G,SHAH R,et al.Chromosome 8q24.1/c-MYC abnormality:a marker for high-risk myeloma[J]. Leuk Lymphoma,2015,56(3):602-607.

细胞遗传学异常类型	例数	超二倍体	非超二倍体
数目和结构异常	30	13	17
仅数目异常	7	5	2
仅结构异常	6	0	6
合计	43	18	25

细胞遗传学异常类型	例数	超二倍体	非超二倍体
数目和结构异常	30	13	17
仅数目异常	7	5	2
仅结构异常	6	0	6
合计	43	18	25

序号	年龄/岁	性别	ISS分期	染色体核型	PFS/年
1	68	女	Ⅲ期	52,X,-X,+3,+5,+7,+9,+15,del（19）（q11）,add（20）（q13）, +21,+mar[4]/46,XX[16]	2.2
2	76	男	Ⅲ期	52~54,XY,+der（1）（q21）,+5×2,del（5）（q21）,der（6）（q23）, +9×2,der（11）（p13）,der（12）（q24）,+19,+20,+21[10]/46, XY[10]	2.7（OS）
3	67	女	Ⅲ期	47,XX,add（4）（q21）,add（5）（p10）,-8,+18,+mar[2]/47,idem, der（3）（q28）[3]/46,XX[19]	1.9
4	54	男	Ⅲ期	54,XY,+6,+7,der（8）（q24）,+9×2,add（11）（p15）,+15, +mar1,+mar2,+mar3[2]/46,XY[22]	2.3
5	58	女	Ⅱ期	46,XX,t（3;17）（q28;q11）[3]/46,XX[17]	1.7
6	83	男	Ⅲ期	46,XY,der（11）（p15）[4]/46,XY[6]	1.5（OS）
7	64	男	Ⅱ期	46,XY,del（12）（p11p12）[2]/46,XY[18]	2.1
8	65	女	Ⅱ期	49,XX,+5,+9,add（12）（p12）,+mar[5]/46,XX[15]	>4.1
9	43	男	Ⅱ期	46,XY,add（10）（q22）,der（12）（q24）[2]46,XY[18]	>3.4

序号	年龄/岁	性别	ISS分期	染色体核型	PFS/年
1	68	女	Ⅲ期	52,X,-X,+3,+5,+7,+9,+15,del（19）（q11）,add（20）（q13）, +21,+mar[4]/46,XX[16]	2.2
2	76	男	Ⅲ期	52~54,XY,+der（1）（q21）,+5×2,del（5）（q21）,der（6）（q23）, +9×2,der（11）（p13）,der（12）（q24）,+19,+20,+21[10]/46, XY[10]	2.7（OS）
3	67	女	Ⅲ期	47,XX,add（4）（q21）,add（5）（p10）,-8,+18,+mar[2]/47,idem, der（3）（q28）[3]/46,XX[19]	1.9
4	54	男	Ⅲ期	54,XY,+6,+7,der（8）（q24）,+9×2,add（11）（p15）,+15, +mar1,+mar2,+mar3[2]/46,XY[22]	2.3
5	58	女	Ⅱ期	46,XX,t（3;17）（q28;q11）[3]/46,XX[17]	1.7
6	83	男	Ⅲ期	46,XY,der（11）（p15）[4]/46,XY[6]	1.5（OS）
7	64	男	Ⅱ期	46,XY,del（12）（p11p12）[2]/46,XY[18]	2.1
8	65	女	Ⅱ期	49,XX,+5,+9,add（12）（p12）,+mar[5]/46,XX[15]	>4.1
9	43	男	Ⅱ期	46,XY,add（10）（q22）,der（12）（q24）[2]46,XY[18]	>3.4