[Diagnostic Value of IGF-I, ß2-MG and SF for Patients with Multiple Myeloma and Their Relationship with Clinical Staging].

OBJECTIVE: To investigate the diagnostic value of insulin like growth factor I(IGF-I), ß2-microglobulin (ß2MG) and serum ferritin (SF) in patients with multiple myeloma (MM) and their ralationship with clinical staging. METHODS: Seventy-seven patients with MM treated in Depertment of Hematology of Shanghai 10th hospital and Oncology of Shanghai Armed Police Hospital from August 2016 to June 2017 were enrolled in MM group, at same period 77 healthy volunteers were enrolled in normal control group. The diagnostic value of IGF-I, ß2-MG and SF for MM, and their levels in different stages of MM were compared. RESULTS: The ROC analysis showed that ß2-MG and SF alone as well as their combination had the diagnostic significance for MM, moreover the diagnostic value of IGF-I, ß2-MG and SF combination was highest, but the single IGF-I did not possess diagnostic significance for MM. The comparison of IGF-I, ß2-MG and SF levels in different stages of MM showed that the ß2-MG and SF levels in I stage were higher than those in normal control group (P<0.05), but lower than those in II and III stages (P<0.05). The IGF-I level in I stage was not statistically and significantly different from IGF-I level in normal control group (P>0.05), but lower than those in II and III stage (P<0.05). The relationship analysis between IGF-I and ß2-MG, SF in different stages showed that the IGF-I related with SF in I stage (r=0.417), but did not relate with ß2-MG; the IGF-I in II stage related with ß2-MG and SF in II stage (r=0.543, r=0.426); IGF-I related with ß2-MG and SF in III stage (r=0.425 and r=0.672). CONCLUSION: The diagnostic value of IGF-I, ß2-MG and SF alone does not high for MM, but their combination can significantly enhance the occurate rate of MM diagnosis. The levels of IGF-I, ß2-MG and SF in II and III stages of MM all increase, moreover the level of IGF-I correlates with the levels of ß2-MG and SF.

[Clinical Significance and Detection Techniques of Minimal Residual Disease in Multiple Myeloma-Review].

The outcomes for the patients with multiple myeloma (MM) have been improved substantially in both progression-free survival and overall survival in the past decade. Many patients are now achieving a complete response to treatments. Extensive data indicate that the information about minimal residual disease (MRD) can be used potentially as a biomarker to evaluate the efficacy of different treatment strategies instead of overall survival. Consequently, highly sensitive assays have been already used in progress for detection of MRD in the patients with MM, such as multiparameter flow cytometry, polymerase chain reaction(PCR), next-generation sequencing and positron emission tomography/computed tomography. This review presents an overview of the clinical significance of MRD in patients with MM and charactemitics of four detection techniques for MRD.

Exome sequencing identifies somatic mutations of DDX3X in natural killer/T-cell lymphoma.

Natural killer/T-cell lymphoma (NKTCL) is a malignant proliferation of CD56(+) and cytoCD3(+) lymphocytes with aggressive clinical course, which is prevalent in Asian and South American populations. The molecular pathogenesis of NKTCL has largely remained elusive. We identified somatic gene mutations in 25 people with NKTCL by whole-exome sequencing and confirmed them in an extended validation group of 80 people by targeted sequencing. Recurrent mutations were most frequently located in the RNA helicase gene DDX3X (21/105 subjects, 20.0%), tumor suppressors (TP53 and MGA), JAK-STAT-pathway molecules (STAT3 and STAT5B) and epigenetic modifiers (MLL2, ARID1A, EP300 and ASXL3). As compared to wild-type protein, DDX3X mutants exhibited decreased RNA-unwinding activity, loss of suppressive effects on cell-cycle progression in NK cells and transcriptional activation of NF-κB and MAPK pathways. Clinically, patients with DDX3X mutations presented a poor prognosis. Our work thus contributes to the understanding of the disease mechanism of NKTCL.

[Inhibiting effect of CaMKIIN up-regulation on leukemia cells growth and its mechanism].

OBJECTIVE: To investigate the inhibitory effects of CaMKIIN on acute myeloid leukemia cell line HL-60 to explore a novel therapeutic target of leukemia. METHODS: Human CaMK II N gene expression vector pcDNA3.1/hCaMKIIN or empty vector pcDNA3.1/myc-His (-) B was transfected into HL-60 cells by Lipofectamine 2000. Human CaMK II N proteins of transfected cells were detected by Western blot. Cell proliferation affected by human CaMKIIN was determined by MTT. Colony-forming assay was performed by soft agar growth system. The cells transfected with CaMKIIN were stained with Hoechst 33342 to detect the apoptotic proportion under fluorescence microscopy. Cell cycle was analyzed by flow cytometry. RESULTS: Human CaMKIIN was stably transfected into HL-60 cells, and overexpression of human CaMKIIN inhibited the proliferation of HL-60/CaMKIIN cells compared to HL-60/mock cells and HL-60 cells [(0.44 ± 0.03) vs (0.94 ± 0.05) vs (0.94 ± 0.04), P<0.01]. The colony formation of HL-60/CaMKIIN was also markedly smaller[(21.00 ± 3.05)/500] than that of mock-transfected [(111.00±4.58)/500]] and control cells [(119.00±6.09)/500] (P<0.01). After 72 hrs-culture, the apoptotic proportion in cells transfected with CaMK II N was obviously higher than of cells transfected with mock DNA or control [(22.49 ± 2.15)% vs (7.17 ± 0.72)% vs (6.40 ± 0.55)%, P<0.01]. Up to (82.97 ± 2.90)% human CaMKIIN/HL-60 cells were arrested at G0/G1 phase, which was more than mock-transfected [(40.53 ± 2.38)%] and control cells [(41.63 ± 2.27)%] (P<0.05). Human CaMKIIN could down-regulate expression of Bcl-2 in transfected cells. CONCLUSION: CaMK IIN up-regulation could inhibit proliferation and induce apoptosis of human acute myeloid leukemia cell HL-60.

[Expression of 11ß-hydroxysteroid dehydrogenase type 2 in lymphoblastic cells and its relationship with glucocorticoid sensitivity].

This study was aimed to explore the expression of 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2) in 3 different lymphoblastic cell lines with relation to their glucocorticoid (GC) sensitivity. The 11ß-HSD2 expressions in acute lymphoblastic leukemia Jurkat cells, lymphoma Daudi and Raji cells, and peripheral blood T cells of a healthy volunteer were analyzed by real time PCR and Western blot. Glucocorticoid (GC)-induced apoptosis in 3 different cell lines was detected by flow cytometry. Cell growth in Jurkat cells treated with cortisol was analyzed by trypan blue dye exclusion. Flow cytometry was performed to observe GC-induced apoptosis in Jurkat cells treated by combination of GC with 11ß-HSD2 inhibition 18ß-glycyrrhetinic acid (18ß-GA). The results demonstrated that 11ß-HSD2 highly expressed in Jurkat cells, but not in Daudi, Raji cells and normal blood T cells. Compared to Daudi and Raji cells, Jurkat cells were more resistant to GC-induced apoptosis. Furthermore, the inhibition of 11ß-HSD2 by 18ß-GA resulted in increased cellular sensitivity to GC as shown by elevated induction of apoptosis. it is concluded that 11ß-HSD2 is at least partly responsible for GC resistance in Jurkat cells. 11ß-HSD2 may be a potential target for reduction of GC-resistance in therapeutic applications.