ABSTRACT
OBJECTIVE@#To explore the renal pathology and cytogenetic features in the multiple myeloma (MM) patients with renal impairment.@*METHODS@#The clinical data of newly diagnosed MM patients with renal impairment in our hospital from January 2009 to January 2019 were analyzed retrospectively, and the relationship between FISH results and results of renal pathological exanimation was analyzed statistically by using SPSS 20.0.@*RESULTS@#A total of 20 patients underwent renal biopsy, included 12 males and 8 females. FISH result showed that out of 20 patients, 7 cases presented interstitial nephritis, among which 3 cases were negative for FISH, and in the remaining cases the rate of IgH rearrangement, 1q21 amplification, RB1 deletion, D13S319 deletion, and P53 deletion detection was 42.86%, 28.57%, 28.57%, 28.57% and 14.29% respectively, the detection positive rate was statistically significantly lower as compared with total probe positive rate (P＜0.01). There were 6 cases of cast nephropathy, among which IgH rearrangement, the rate of 1q21 amplification, RB1 deletion, D13S319 deletion, and P53 deletion detection was 66.67%, 50%, 66.67%, 50% and 0% respectively. Compared with the total probe positive rate, there was no statistical significance (P＞0.05). There were 4 cases of acute tubular necrosis, among which the detection rates of IgH rearrangement, 1q21 amplification, RB1 deletion, D13S319 deletion, and P53 deletion was 100%, 50%, 50%, 25% and 25%, respectively. Compared with the total probe positive rate, there was no statistical significance (P＞0.05). There were one case of amyloidosis, and one case of tubular nephropathy with amyloidosis, the detection with 5 probes were all positive. One case of light chain deposition disease was positive for RB1 gene deletion + D13S319 gene deletion.@*CONCLUSION@#FISH in the MM patients with different renal pathological changes is characterized by heterogeneity, which can be used to predict the risk of renal damage and speculate possible renal pathological types to guide prognosis.
Subject(s)
Female , Humans , Male , Chromosome Aberrations , Cytogenetic Analysis , Cytogenetics , In Situ Hybridization, Fluorescence , Multiple Myeloma , Retrospective StudiesABSTRACT
OBJECTIVE@#To investigate the mechanism of rapamycin-induced apoptosis of chronic myelogenous leukemia cells.@*METHODS@#The chronic granulocytic leukemia K562 cells were divided into 3 groups: A, B and C group were treated with rapamycin of 10, 15 and 20 nmol/L, repectively for 24 h, while the K562 cells in control group were not treated with rapamycin. The effect of rapamycin on the proliferation of K562 cells was detected by MTT, and the effect of rapamycin on the apoptosis of K562 cells was detected by AnnexinV-FITC/PI double staining. The expression level of EZH2/Hedgehog signaling pathway genes in K562 cells was detected by RT-PCR, and Western blot was used to detect the levels of apoptotic protein and the related signaling pathway proteins in K562 cells.@*RESULTS@#The MTT assay showed that the different concentration of rapamycin had obvious inhibitory effects on the cells, and the survival rate of cells in group C was 37.6%±3.4%, which was significantly lower than that of the other groups (P＜0.05). The apoptosis rate of cells in group C was 93.1%±8.1%, which was significantly higher than that of the other groups (P＜0.05). By Western blot, it was found that the relative expression levels of Caspase-3 and BAX protein in group C were 0.36 ± 0.04 and 0.39±0.06, respectively, which were significantly higher than those in other groups (P＜0.05), and the level of BCL-2 protein was 0.17±0.03, which was significantly lower than that of other groups (P＜0.05). By RT-PCR, it was found that the mRNA levels of EZH2 and Hedgehog genes in A, B and C groups were significantly lower than those in the control group (P＜0.05), but mRNA level of Ptch1 gene was significantly higher than that of the control (P＜0.05). By Western blot, it was found that the expression levels of EZH2 and Hedgehog protein in A, B and C groups were significantly lower than that in the control group (P＜0.05), but the level of Ptch1 protein was higher than that of the control (P＜0.05). The relative levels of EZH2 and Hedgehog protein in group C were 0.21 ±0.03 and 0.16±0.05 respectively, which were significantly lower than those in other groups (P＜0.05), and Ptch1 protein level were 0.46 ±0.06, significantly higher than that of other groups (P＜0.05).@*CONCLUSION@#Rapamycin can inhibit the protein expression of EZH2 in leukemic cells, thus interfere with the activation of Hedgehog signaling pathway, promote the expression of apoptotic protein, reduce the level of anti apoptotic protein, and eventually induce apoptosis of leukemia cells.