PDGFRβ基因检测在血液肿瘤中的临床应用

Clinical significance of PDGFRβgene testing in hematological tumors

目的探讨伴有血小板衍生生长因子β(PDGFRβ)基因不同类型异常的血液系统肿瘤的临床及实验室特征。方法回顾性分析海军军医大学附属长海医院2009年至2020年间带有5号染色体长臂(5q)异常且病史资料较为全面的141例病例,收集其临床资料。运用染色体R带显带技术对患者骨髓进行染色体核型分析,并运用荧光原位杂交技术(FISH)进行PDGFRβ基因检测。收集检测结果,按荧光原位杂交信号结果分为扩增组、缺失组及易位组。对三组数据列交叉表进行统计分析,若样本容量n≥40且每格预期频数T均≥5,则使用Pearson卡方检验对三组数据进行组间比较;若n<40或任意一格预期频数T<5,则使用Fisher精确检验。若三组数据组间比较结果有差异,则进一步使用Bonferroni法对三组数据进行两两比较。结果PDGFRβ探针检测出PDGFRβ基因异常患者共98例,检出率为69.50%(98/141)。其中PDGFRβ基因扩增组38例(38.78%,38/98)、缺失组57例(58.16%,57/98)、易位组3例(3.06%,3/98)。98例病例中检出复杂核型93例,其中扩增组为37例(97.37%,37/38),缺失组为55例(96.49%,55/57),易位组为1例(33.33%,1/3)。分析三组的临床资料,PDGFRβ缺失组、扩增组与易位组无明显性别优势(P>0.05)。PDGFRβ缺失组以髓系肿瘤为主(P<0.001),如急性髓细胞白血病(AML)及骨髓增生异常综合征(MDS)等,PDGFRβ扩增组更多见于淋系肿瘤(P<0.001),如多发性骨髓瘤(MM)等,PDGFRβ易位组均见于骨髓增生异常/骨髓增殖性肿瘤(MDS/MPN)。结论伴有PDGFRβ基因重排的肿瘤兼有骨髓增殖性肿瘤(MPN)的过度增殖和MDS的病态造血改变,具有典型的临床和血液学特征。伴有PDGFRβ基因异常的肿瘤是一种较少见的血液系统肿瘤,除了以往髓系肿瘤MPN或MDS/MPN,也可覆盖于多发性骨髓瘤、非霍奇金淋巴瘤等淋巴/浆细胞肿瘤。

Objective To explore the clinical and laboratory characteristics of hematological tumors with different types of abnormalities in platelet derived growth factorβ(PDGFRβ)gene.Methods A retrospective analysis was carried out on 141 patients with abnormal long arm of chromosome 5(5q)and comprehensive medical history data from Changhai Hospital Affiliated to Naval Medical University from 2009 to 2020,and their clinical data were collected.R-banding technique was used for chromosomal karyotyping analysis for the patient′s bone marrow,and fluorescence in situ hybridization(FISH)was used to detect the PDGFRβgene.The results of detection were divided into the amplification group,deletion group,and translocation group based on FISH signals.The three sets of data column crosstabs were statistically analyzed,and if the sample size was n>=40 and the expected frequency T for each cell was>=5,a Pearson test was used to compare the three groups of data.If N<40 and any of the expected frequency T for each cell was<5,a Fisher′s exact test is used.Should there be a difference in the comparison results between the three sets of data,a Bonferroni method was further used to compare the data.Results In total 98 patients were detected to have PDGFRβgene abnormalities with the PDGFRβprobe,which yielded a detection rate of 69.50%(98/141).Among these,38 cases(38.78%)had PDGFRβgene amplifications,57 cases(58.16%)had deletions,and 3(3.06%)had translocations.Among the 98 cases,93 were found to have complex karyotypes,including 37 cases from the amplification group(97.37%,37/38),55 cases from the deletion group(96.49%,55/57),and 1 case from the translocation group(33.33%,1/3).Analysis of three sets of clinical data showed no significant gender preponderance in the groups(P>0.05).The PDGFRβdeletion group was mainly associated with myeloid tumors,such as acute myeloid leukemia(AML)and myelodysplastic syndrome(MDS)(P<0.001).The PDGFRβamplification group was more common in lymphoid tumors,such as multiple myeloma(MM)(P<0.001).The PDGFRβtranslocation group was also more common in myelodysplastic/myeloproliferative tumors(MDS/MPN).Conclusion Tumors with PDGFRβgene rearrangement may exhibit excessive proliferation of myeloproliferative tumors(MPN)and pathological hematopoietic changes in the MDS,and have typical clinical and hematological characteristics.As a relatively rare type of hematological tumor,in addition to previously described myeloid tumors such as MPN or MDS/MPN,it may also cover lymphoid/plasma cell tumors such as multiple myeloma and non-Hodgkin′s lymphoma.