Genetic Abnormalities And Survival In Multiple Myeloma: A Study Of 60 Cases In China

Objective To summarize the molecular cytogenetic aberrations and clinical significance of 60 multiple myeloma(MM) patients detected by interphase fluorescence in situ hybridization(i-FISH) and conventional cytogenetics(CC).Methods Specimens of bone marrow were collected from 60 patients with MM who visited the Institute of Hematology and Blood Diseases Hospital,Chinese Academy of Medical Sciences in Tianjin,China.I-FISH analysis combined with magnatic-activited cell sorting(MACS) were performed on four specific probes for the regions containing 13q14(RB-1/D13S319),14q32(IGH),17p13(P53) and 1q21.And the i-FISH studies with LSI IGH/CCND1,LSI IGH/FGFR3,LSI IGH/MAF probes were used to detect t(11;14)(q13;q32),t(4;14)(p16;q32) and t(14;16)(q32;q23) in patients with 14q32 rearrangement.Results(1) i-FISH was used to investigate 60 patients with MM,whose median age was 56 years.Of the 60 patients investigate by i-FISH whose molecular cytogenetic aberrations were found in 52(86.7%) patients.6(10%) patients simultaneously had 13q deletions/monosomy 13(A13),illegitimate IGH rearrangement,17p deletions and chromosome 1q amplification.Δ13 was detected in 32(53.3%) cases,IGH rearrangement in 40(66.7%) cases including 19 with t(11;14) and 13 with t(14;16) and 3 with t(14;16),17p deletions was detected in 15(25%) cases and 32(56.1%) with 1q amplification.(2)30 cases were detected by both conventional FISH and i-FISH combined with MACS.Compaired the detectinon rate of the two group,the latter was much higher than the former.(P=0.008)(3)According to the Mayo Clinc study,we divided the newly diagnosed cases in two groups:standard-risk and high-risk,And there were significant differences of PFS between them.(P=0.007)(4)Univariate analysis showed that 17p deletions,β₂-MG＞5.5mg/l,plasma cell percentage were associated with significantly shorter PFS.Multivariate analysis indicated that only 17p deletions was the independent unfavorable factor.(5)Compaired with traditional chemotherapy,bortezomib can significantly improved the short-term effect of patients withΔ13,IGH rearrangement, 1q amplification but not 17p deletions.Conclusions(1)i-FISH combined with MACS is a very effective way to analyse the molecular cytogenetic aberrations of MM.(2) Mayo Clinc stratification can give a good guidance to the treatment of MM patients.(3)Univariate analysis showed that 17p deletions,β₂-MG＞5.5mg/l,plasma cell percentage were associated with significantly shorter PFS.Multivariate analysis indicated that only 17p deletions was the independent unfavorable factor.