Prognostic power of abnormal cytogenetics for multiple myeloma: a multicenter study in China.

BACKGROUND: Chromosomal abnormalities have been shown to play an important prognostic role in multiple myeloma (MM). Interphase fluorescence in situ hybridization (i-FISH) has been much more effective to identify cytogenetic aberrations in MM than conventional cytogenetic technique (CC). To clearly determine the cytogenetic features of Chinese MM patients and identify their prognostic implications, we designed a multicenter study based on i-FISH including 672 patients from 52 hospitals in China. METHODS: All 672 patients were systematically screened for the following genomic aberrations: del(13q), IgH rearrangement, del(p53) and 1q21 amplifications. RESULTS: The analysis showed that the chromosomal changes were detected in 22.1% patients by CC and in 82.3% patients by i-FISH. The most common abnormalities by CC were chromosome 1 aberrations (48.4%), -13/13q- (37.6%), hyperdiploidy (36.6%), hypodiploidy (30.1%) and IgH rearrangements (23.7%). The most frequent abnormalities by FISH was del(13q), which was found in 60.4% patients, whereas IgH rearrangement, 1q21 amplification and p53 deletions were detected in 57.6%, 49.0% and 34.7% cases, respectively. By statistical analysis, -13/13q- by CC was associated with low level of platelet (P = 0.015), hyperdiploidy was associated with low level of serum albumin (P = 0.028), and IgH rearrangement by FISH was associated with high level of ß2 microglobulin (P = 0.019). Moreover, 1q21 amplification and del(p53) by FISH conferred a high incidence of progressive disease (PD) after initial therapy. Metaphase detection of IgH rearrangements and chromosome 1 aberrations concurrently was associated with a short progression free survival (PFS) (P = 0.036). No significant prognostic implications of other cytogenetic abnormalities were found associated with overall survival and PFS. CONCLUSIONS: Chinese MM patients had similar cytogenetic abnormalities compared with the previous reported studies. However, the prognostic significance of FISH aberrations were not clearly determined and further study is required.

[Identification of a novel lymphotoxin-alpha (LTA) gene associated with ankylosing spondylitis in Ningxia population].

Lymphotoxin-alpha (LTA) gene has been reported to have a genetic association with systemic lupus erythematosus (SLE), psoriasis, and rheumatoid arthritis. However, the association of LTA with ankylosing spondylitis (AS) has not reported. By case-control study, we carried out the high density limited genome scanning to the HLA class III region about 58 kb in Ningxia population (case 300 and control 385). In this study, 33 SNPs in LTA were genotyped in Ningxia population. We analyzed these SNPs and the haplotypes covering LTA. Only the distribution of TCC haplotype which contains mutation allele of LTA rs909253 was statistically significant(P=0.0005). The C allele frequency of the LTA rs909253 T/C polymorphism was higher in AS cases than that in the controls (28.5% versus 19.7%, P=2×10-4) in Ningxia population. The results suggest that there is a relevance between LTA and the susceptibility of AS, and we identified that the LTA polymorphism may be associated with AS in Ningxia population.