Bortezomib (BTZ), being the first proteasome inhibitor, has been applied widely in clinic. Through combining with targeting β5 subunit/chymotrypsin-like and inhibiting the activity of proteasome reversibly, BTZ manages to inhibit intracellular degradation of protein, thus inducing apoptosis of myeloma cells. Since 2000, when BTZ was approved by Food and Drug Administration (FDA) for treatment of multiple myeloma (MM), both response rates and long-term survival time of these patients have been improved significantly. However, most patients will inevitably end up with relapse or drug resistance due to its high heterogeneity. Thus, it is of great necessity to explore the mechanism as well as overcome BTZ resistance. This review aims to summarize the current researches available on mechanisms of BTZ resistance in MM.

Objective To explore the prognostic impact of miR137 target gene Kruppel-like transcription factor 12 (KLF12) in multiple myeloma (MM). Methods The target genes of miR137 were predicted by software. The GFP analysis of KLF12 and the prognosis of MM were constructed. Overexpressing miR137 in MM NCI-H929 cell line was also constructed. Real-time qPCR and Western blot were used to detect the expression of KLF12 in this cell line. Results The target genes of miR137 were MITF, BUE2H, SH3BP5 and KLF12. High expression of KLF12 in 455 patients included 75 patients (16.5 %) died, 104 patients with low expression of KLF12, and 25 patients (24.0 %) died, but no significance was detected in the different subgroups. KLF12 expression was higher in MM NCI-H929 cell line with miR137 over expression. The expression of miR137 was positively correlated with the expression of KLF12. Conclusion miR137-KLF12 is an important index to judge the prognosis of MM.

Objective: To investigate the clinical efficacy and safety of lenalidomide (Revlimid, R) -based chemotherapy in the treatment of relapsed/refractory multiple myeloma (MM) patients. Methods: 57 consecutively relapsed/refractory MM patients were retrospectively analyzed from June 2013 to February 2016. All the patients received lenalidomide-based chemotherapy. Results: ① 60.4% patients had international staging system (ISS) stage Ⅲ, 37.9% patients had revised international staging system (R-ISS) stage Ⅲ, and 53.3% patients harbored at least one of the high-risk cytogenetic abnormalities[del (17p) and/or t (4;14) and/or t (14;16) ]. ②The patients received median 6 cycles of R (range: 1-32). The overall response rate (ORR) was 58.9% (33/56) , among which 8.9% was complete response (CR) , 19.8% was very good partial response (VGPR) , and 30.4% was partial response (PR). In addition, 10.7% patients attained minor response (MR). Total clinical benefit was 69.6%. Patients with more than 1 line of prior therapy, or previously thalidomide-resistance, or R-ISS stage Ⅲ disease showed significantly lower ORR. ③With a median follow-up of 27 months, the median progression free survival (PFS) , the median interval to PR, the median duration of response (DOR) , and the median overall survival (OS) was 8 months, 2 months, 8 months, and 19 months, respectively. Univariate prognostic analysis showed that abnormal karyotype, R-ISS stage Ⅲ and response inferior to PR were negative prognostic factors for PFS and OS. While the multivariate prognostic analysis showed that abnormal karyotype and R-ISS stage Ⅲ were independent prognostic factors. ④In the safety aspect, the most common grade 3-4 non-hematology adverse events (AEs) were infection (17.5%) , rash (1.8%) and thromboembolism (1.8%) , and the most common grade 3-4 hematology AEs were neutropenia (7.0%) and thrombocytopenia (3.5%). Totally 3 patients (5.3%) discontinued R because of AEs, and 2 cases (3.5%) of secondary primary malignancies were observed. Conclusion The R-based treatment is effective and safe in the treatment of relapsed/refractory MM patients in China. Abnormal karyotype and R-ISS stage Ⅲ were independent negative prognosis factors in this cohort.

In recent years,several large-scale clinical trials have confirmed that lenalidomide has a certain role in the treatment of non-Hodgkin lymphoma (NHL).Currently,the latest edition of the National Comprehensive Cancer Network (NCCN)guideline (2018.V3) recommend that lenalidomide could be used for multiple subtypes of NHL including diffuse large B-cell lymphoma,mantle cell lymphoma,follicular lymphoma,and marginal zone lymphoma.This article reviews the progress in the application of lenalidomide in NHL.

Multiple myeloma (MM) is a clonal malignancy characterized by the infiltration of clonal plasma cells in the bone marrow and monoclonal M protein in peripheral blood and urine. MM can be divided into smoldering multiple myeloma (SMM) with no obvious symptoms and active MM which can be diagnosed according to the end-organ damaging caused by clonal proliferation of plasma cells. When it happens, the patients need to receive systematic treatment. SMM patients without high risk factors merely need the routine observation and following-up. Therefore, right diagnosis and differential diagnosis are related with the indication and timing of treatment. Besides, MM is a very heterogeneous disease with overall survival from a few months to more than ten years. Accurate risk stratification in the initial diagnosis plays a key role in realizing individual treatment and improving prognosis.