| Objective: To detect the incidence of chromosomal abnomalities in patients with multiple myeloma(MM)by using flurorescence in situ hybridization(FISH)technology,analyze the relationships between FISH detection and sex,age,type,stage and other laboratorial data,and discuss its clinical significances.Methods: Bone marrow samples of 66 initial diagnosed multiple myeloma patients were collected from 2013-02-01 to 2017-01-01.Myeloma cells were gathered by magnetic activated cell sorting,and then we used 8 specific probes(including 1q21 ? MAF ? TP53 ? D13S319 IGH/MAF ?IGH/FGFR3 ? IGH/CCND1)to detect the incidence of chromosomal abnormalities in patients with multiple myeloma.Results: 1 FISH results 1.1 The incidence of chromosomal abnormalities: 66 multiple myeloma patients were detected by FISH technology and the percentage of overall abnormalities was 83.3%(55/66).The figure for more than 2 probes was 56.1%(37/66),while 17 chromosome accounted for 12.1%(8/66)by using TP53 probe.Chromosome 14 abnormalities were detected by IGH probes and the positive chromosome abnormalities accounted for 54.5%(36/66):the positive percentage of IGH/MAF was 3.0%(2/66)and the figure for IGH/FGFR3 was 13.6%(9/66),IGH/CCND1 25.8%(17/66).D13S319 were used to detect chromosome 13 and 40.9% of patients' D13S319 were positive(27/66).The positive percentage of 1q21 amplification was 47.0%(31/66).1.2 The relationship between D13S319 and IGH: The D13S319 was related with the rearrangement of IGH(P=0.020<0.05),and other genes were not related with each other.1.3 The relationship between the chromosomal abnormalities and clinical indicators: The 1q21 amplification was related with decreasing of hemoglobin(HGB)(P=0.028);TP53 was associated with high level of LDH(P=0.041),and the infection of first chemotherapy(P=0.017);D13S319 correla ted with high age(P=0.020);IGH/CCND1 correlated with the bone fusi on's increasing(P=0.003)and albumin's(ALB)declining(P=0.049).IGH/FGFR3 was related with ALB's decreasing(P=0.010).Other genes were unrelated with the clinical data.2 FISH results and MM patients' survival 13 cases(19.7%)were died when we followed up to January 1st,2017.Kaplan-Merer method was used to count the survival rates and draw the survival chart.TP53 postive(8 cases)and negative's(53cases)OS were 28.250 and 42.605 months respectively,and PFS were 17.857 and 28.415 months respectively by using single analysis,which was significant(P=0.027 and P=0.045).1q21 postitive' PFS(31 cases)was shorter than that of 1q21 nagative(30 cases),which was 21.017 and 31.896 months respectively and there were significant difference between the two groups(P=0.022);however,1q21's OS was not statistically significant(P=0.622);The OS of IGH/FRFR3 abnormalities(9 cases)and normalities(50 cases)were 17.889 and 41.672 months,while the PFS of them were 12.063 and 28.757 months,and differences were both seen among them(P=0.037 and P=0.025).There was no differences(P=0.137)about OS between IGH/MAF abnormalities(2 cases)and normalities(57 cases);however,their PFS were 4.000 and 28.518 months respectively and had significant difference(P=0.000).D13S319 abnormalities(25 cases)and normalities(36 cases)were 39.926 and 37.926 months,while the PFS of them were 28.466 and 19.270 months,and differences were not both seen among them(P=0.700 and P=0.182).When we divided 61 patiens to three groups:1q21 nagative,only 1q21 postive and 1q21 postive and other abmormalities,we found that their OS were 43.618,24.314 and 13.500 months and had no difference(P>0.05);while PFS were 31.896,20.400 and 8.125 months,there was difference between 1q21 nagative and only 1q21 postive group(P=0.038)and differences were not significant among other groups(P>0.05).3 Clinical data and patient's survival 3.1 ISS,R-ISS stages and survival: According to ISS stage,the OS of?(5 cases),?(23 cases)and ?(38 cases)were 41.000?34.436 and 35.775 months respectively,and the PFS of them were 23.250 ? 27.647 and 25.768 months.There were no significant difference among OS and PFS of ISS stages(P=0.918 and P=0.918).According to R-ISS stage,while the OS of?(5 cases),?(47 cases)and ?(14 cases)were 47.022?37.585 and 20.674 months respectively,the PFS of them were 23.250?30.005 and 13.464 months and PFS of ? stage was remarkablely shorter than that of?/? stages,which differences were both significant(P=0.039 and P=0.000);According to m SMART,OS of low risk stage were 41.771 months> median risk 38.599 months>high risk 22.111 months,PFS of low risk stage 31.055 months>20.045 months>16.375 months,and high risk of PFS was shorter than low risk stage,which were both significantly different(P=0.036 and P=0.010).3.2 Clinical indicators and survival: The OS of those whose HB <100g/L and ?100g/L were 31.862 and 44.324 months,and difference was not found(P=0.136);the figure for PFS were 20.935 and 30.552 months,and there was significant difference(P=0.020).The OS of those whose PLT <100×109/Lwas shorter than that of PLT?100×109/L,which were 11.906 and 43.738 months,and difference was significant(P=0.000);the figure for PFS were 15.641 and 28.029 months,and difference was not significant(P=0.069).The OS and PFS of those whose LDH?225U/L was shorter than LDH<225U/L,while the OS were 23.375 and 44.601 months and the PFS were 15.631 and 29.217 mouths,which were different(P=0.003 and P=0.002).The figure for OS of those who had infection after first chemotherapy was shorter than that of those who had no infection,which were 30.236 ? 47.917 months,and had significant difference(P=0.005);difference was not significant about PFS(P=0.673).3.3 By using Cox regression analysis,we found the high risk stage of m SMART?plasma cell?30%?PLT<100×109/L?ALB<35g/L?LDH?225U/L were related with the short OS;R-ISS? stage?HB <100g/L?PLT<100×109/L?Cr?175umol/L?infection of first chemotherapy were associated with short PFS.Conclusions: 1 The most common gene abnormality was IGH translocation and chromosome abnormalities were often found in 14,1 and 13 chromosome when FISH technology was used to detect patients.2 The D13S319 was related with IGH/FGFR3.3 The 1q21 amplification was related with decreasing of hemoglobi n(HGB);TP53 was associated with high level of LDH,and the infecti on of first chemotherapy;D13S319 correlated with high age;IGH/CCN D1 correlated with the bone fusion's increasing and albumin's(ALB)de clining.IGH/FGFR3 was related with ALB's decreasing.Other genes wer e unrelated with the clinical data.4 TP53,IGH/FGFR3 and IGH/MAF were adverse prognostic factors,and their OS and PFS were different;There were no differences about OS and PFS.While there were significant difference between 1q21 postitive and 1q21 nagative about PFS,difference was also seen about PFS between 1q21 nagative and only 1q21 postive group and differences were not significant about OS.5 ISS stage were no significantly different among OS and PFS.According to R-ISS stage,differences were both significant;According to m SMART,high risk of PFS and OS were shorter than low risk stage,which were significantly different.6 The difference was not found about OS of those whose HB <100g/L and ?100g/L;the figure for PFS was significant different.The OS of those whose PLT<100×109/Lg/L was significantly different and PFS were not different.The OS and PFS of those whose LDH?225U/L was shorter than LDH<225U/L were different.The figure for OS of those who had infection after first chemotherapy had significant difference;difference was not significant about PFS.7 By using Cox regression analysis,we found the high risk stage of m SMART?plasma cell?30%?PLT<100×109/Lg/L?ALB<35g/L?LDH? 225U/L were related with the short OS;R-ISS? stage?HB <100g/L?PLT<100×109/L?Cr?175umol/L?infection of first chemotherapy were associated with short PFS. |
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