Investigation Of Molecular Cytogenetics In Patients With Multiple Myeloma Using Interphase Fluorescence In Situ Hybridization

ObjectiveMultiple myeloma (MM) is an incurable hematological disorder characterized by the accumulation of malignant plasma cells within the bone marrow (BM). Its incidence is about 10%. The clinical heterogeneity of MM is decided by the cytogenetic aberrations of MM. Cytogenetic studies in MM are hampered due to the hypoproliferative property of plasma cells in MM. Therefore, interphase fluorescence in situ hybridization (I-FISH) analysis combined with CD138 immunomagnetic cell sorting (MACS) is an attractive alternative for evaluation of numerical and structural chromosomal aberrations in MM. Our study is to investigate the incidence and prognosis of 1q21 amplification, 13q14 deletion, TP53 gene deletion and IgH translocation in patients with MM, and further to investigate the curative effect of Thalidomide and Bortezomib.MethodI-FISH studies with four different specific probes for the regions containing 1q21, 13q14.3 (D13S319), 14q32 and TP53 gene were performed in 58 MM patients. The probes of LSI IGH/CCND1, LSI IGH/FGFK3 and LSI IGH/MAF were used to detect t(11;14)(q13;q32), t(4;14)(p16.3;q32) and t(14;16) (q32;q23) in patients with 14q32 rearrangement.ResultsAmong 58 patients with MM, 1q21 amplification was determined in 37 (63.8%) cases, 13q14 deletion in 40 (69%) cases, TP53 gene deletion in 11 (19%) cases, and IgH translocation in 35 (60.3%) cases. Among 33 MM patients with IgH translocation, 18 (54.5%) cases harbored t(11;14), 12 (36.4%) cases harbored t(4;14), 4 (12.1%) cases harbored t(14;16),only one patient with both t(4;14) and t(14;16). The mortality of MM patients with 1q21 amplification,13q14 deletion or TP53 gene deletion was higher than those without them. The mortality of MM patients with t(11;14) was lower than those with t(4;14) and t(14;16). Thalidomide could improve the rates of complete remission (CR) and partial remission (PR) on MM patients with TP53 gene deletion. Bortezomib could improve the rates of CR and PR on MM patients with 1q21 amplification, 13q14 deletion and t(11;14).ConclusionThe frequency of 1q21 amplification,13q14 deletion, TP53 gene deletion and IgH translocation in multiple myeloma is high; 1q21 amplification,13q14 deletion, TP53 gene deletion and t(4;14) are poor prognosis factors. Thalidomide could improve the prognosis of MM patients with TP53 gene deletion. Bortezomib could improve the prognosis of MM patients with 1q21 amplification and 13q14 deletion. Objective:Chromosome 1 aberration is very common in multiple myeloma(MM). Its incidence is approximately 49%. The study of chromosome 1 aberration is contributed to reveal clinical progression and prognosis of patients with multiple myeloma, and is assistant to choose optimal treatment program. In this study, we investigated the incidence of 1q21 amplification and 1p12 deletion. We also analyzed the correlation between chromosome 1 aberration and the progression of diease or prognosis in patients with MM.Method:Cytoplasmic light chain immunofluorescence with simultaneous interphase fluorescence in situ hybridization (cIg-FISH) was applied to detected the 1q21 amplification and 1p12 deletion in 48 patients with MM.Results:1q21 amplification (≥3 red signals) was determined in 26 of 48(54.2%) cases, 10 with 3 red signals and 16 with≥4 red signals; 1p12 deletion (<2 green signals) was determined in 14 of 48 (29.2%) cases. The mortality of patients with 1q21 amplification were significantly higher than that in MM lacking 1q21 amplification (P<0.05). The sex, age, D-S stage,subgroup and ISS stage in patients with 1q21 amplification had no significant difference compared with in those without 1q21 amplification (P>0.05). Further study showed that there were significant difference of D-S stage and mortality between patients with 3 copies of 1q21 and those with at least 4 copies of 1q21 (P<0.05). However no significant difference of sex, age, subgroup, ISS stage, and isotype was found between them (P>0.05). There was no significant difference of sex, age, D-S stage, ISS stage, isotype, subgroup, and mortality in patients with 1p12 deletion compared with those lacking 1p12 deletion. There was a strong correlation between CD138 MACS in combination with I-FISH and cIg-FISH (P>0.05).Conclusion:The frequency of chromosome 1 aberration in multiple myeloma is high, 1q21 amplification is a poor prognosis factor. The prognosis of patients with at least 4 copies of 1q21 was worse than those with 3 copies of 1q21. Objective:To explore the value of the technique of multiplex fluorescence in situ hybridization (M-FISH) in the detection of the complex chromosomal aberrations (CCAs) in multiple myeloma (MM).Methods :M-FISH was used in ten MM patients with CCAs detected by conventional cytogenetics (CC) using R-bandig to refine the rearrengement of CCAs and identify characterization of marker chromosomal.Results :M-FISH confirmed the 29 structural aberrations showed by CC analysis, and also confirmed the specific source of 21 kinds of chromosomal aberrations, which were undetected or unidentified by CC analysis. t(2;15)(q33;q22),t(6;7)(q23;q34),t(8;11) (q24;q23),t(1;14)(q10;q32) and t(X;1)(q26;q25) are new chromosomal aberrations we detected. The median survival time of nine MM patients with CCAs was 23 months and evident shorter than that of MM patients without CCAs, the mean survival time was 34 months received.Conclusion: M-FISH could refine CCAs of MM patients, find or correct the missed or misidentified abnormalities analyzed by CC. It has provided one of the essential methods for the research of chromosomal aberrations in MM.