Comparison of the Efficacy Among Nilotinib, Dasatinib, Flumatinib and Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia Patients: A Real-World Multi-Center Retrospective Study.

BACKGROUND: There are limited data comprehensively comparing therapy responses and outcomes among nilotinib, dasatinib, flumatinib and imatinib for newly diagnosed chronic-phase chronic myeloid leukemia in a real-world setting. PATIENTS AND METHODS: Data from patients with chronic-phase CML receiving initial a second-generation tyrosine-kinase inhibitor (2G-TKI, nilotinib, dasatinib or flumatinib) or imatinib therapy from 77 Chinese centers were retrospectively interrogated. Propensity-score matching (PSM) analyses were performed to to compare therapy responses and outcomes among these 4 TKIs. RESULTS: 2,496 patients receiving initial nilotinib (n = 512), dasatinib (n = 134), flumatinib (n = 411) or imatinib (n = 1,439) therapy were retrospectively interrogated in this study. PSM analyses indicated that patients receiving initial nilotinib, dasatinib or flumatinib therapy had comparable cytogenetic and molecular responses (p = .28-.91) and survival outcomes including failure-free survival (FFS, p = .28-.43), progression-free survival (PFS, p = .19-.93) and overall survival (OS) (p values = .76-.78) but had significantly higher cumulative incidences of cytogenetic and molecular responses (all p values < .001) and higher probabilities of FFS (p < .001-.01) than those receiving imatinib therapy, despite comparable PFS (p = .18-.89) and OS (p = .23-.30). CONCLUSION: Nilotinib, dasatinib and flumatinib had comparable efficacy, and significantly higher therapy responses and higher FFS rates than imatinib in newly diagnosed CML patients. However, there were no significant differences in PFS and OS among these 4 TKIs. These real-world data may provide additional evidence for routine clinical assessments to identify more appropriate therapies.

MUC20 regulated by extrachromosomal circular DNA attenuates proteasome inhibitor resistance of multiple myeloma by modulating cuproptosis.

BACKGROUND: Proteasome inhibitors (PIs) are one of the most important classes of drugs for the treatment of multiple myeloma (MM). However, almost all patients with MM develop PI resistance, resulting in therapeutic failure. Therefore, the mechanisms underlying PI resistance in MM require further investigation. METHODS: We used several MM cell lines to establish PI-resistant MM cell lines. We performed RNA microarray and EccDNA-seq in MM cell lines and collected human primary MM samples to explore gene profiles. We evaluated the effect of MUC20 on cuproptosis of PI-resistant MM cells using Co-immunoprecipitation (Co-IP), Seahorse bioenergetic profiling and in vivo assay. RESULTS: This study revealed that the downregulation of Mucin 20 (MUC20) could predict PI sensitivity and outcomes in MM patients. Besides, MUC20 attenuated PI resistance in MM cells by inducing cuproptosis via the inhibition of cyclin-dependent kinase inhibitor 2 A expression (CDKN2A), which was achieved by hindering MET proto-oncogene, receptor tyrosine kinase (MET) activation. Moreover, MUC20 suppressed MET activation by repressing insulin-like growth factor receptor-1 (IGF-1R) lactylation in PI-resistant MM cells. This study is the first to perform extrachromosomal circular DNA (eccDNA) sequencing for MM, and it revealed that eccDNA induced PI resistance by amplifying kinesin family member 3 C (KIF3C) to reduce MUC20 expression in MM. CONCLUSION: Our findings indicated that MUC20 regulated by eccDNA alleviates PI resistance of MM by modulating cuproptosis, which would provide novel strategies for the treatment of PI-resistant MM.

Long noncoding RNA LINC00675 drives malignancy in acute myeloid leukemia via the miR-6809 -CDK6 axis.

Hematological malignancies such as acute myeloid leukemia (AML) have a low cure rate and a high recurrence rate. Long noncoding RNAs (LNCs) are essential regulators of tumorigenesis and progression. The role of lncRNA LINC00675 in AML has rarely been reported. This study revealed elevated LINC00675 expression in AML that promotes proliferation and inhibits apoptosis. Mechanistically, LINC00675 combines with miR-6809 to promote the expression of CDK6 in vitro and in vivo. Immune-checkpoint genes were expressed more highly in LINC00675-high patients. A high level of LINC00675 expression may make patients more susceptible to palbociclib treatments. In conclusion, our study demonstrated that LINC00675 is an oncogenic lncRNA that enhances the malignancy of AML by upregulating CDK6 expression through miR-6809 sponging, providing a new perspective and feasible target for the diagnosis and treatment of AML.

Decitabine in patients with myelodysplastic syndromes: A multi-center, open-label, dose comparison trial.

BACKGROUND: The hypomethylating agent decitabine is the standard therapy for intermediate or high risk myelodysplastic syndrome (MDS). METHODS: In this trial, 191 adult patients with intermediate/high risk MDS (IPSS score ≥ 0.5) randomly received decitabine using a standard regimen (20 mg/m2 /day for 5 consecutive days; n = 94) or an extended regimen with lower daily dose (12 mg/m2 /day for 8 consecutive days; n = 97) every 4 weeks, for a total of 4 cycles. RESULTS: The median follow-up was 14 months (range 2-36). The primary end point of overall response rate in the intent-to-treat analysis was 41.5% and 38.1% in the standard and extended dosing arms, respectively (p = 0.660). Complete remission and marrow complete remission also did not differ between the two arms. Cytopenia was the most frequent adverse event (76.4%). The median duration of neutropenia per cycle did not differ between the two arms during the first two cycles, but significantly shorter in the extended dosing arm in the third cycle (8.5 vs. 15.5 days, p = 0.049) and in the fourth cycle (8 vs. 14 days, p = 0.294). CONCLUSION: The 5-day 20-mg/m2 /day and 8-day 12-mg/m2 /day decitabine regimens have similar efficacy and safety in patients with intermediate or high risk MDS.

Patient-Reported Outcomes in Young Adults with Myeloproliferative Neoplasms.

INTRODUCTION: Genetic landscape, disease characteristics, and clinical outcomes of young adults with myeloproliferative neoplasms (MPNs) were reported. However, data on patient-reported outcomes (PROs) in young adults with MPNs were rare. METHODS: We conducted a multicenter, cross-sectional study to compare the PROs in respondents with thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF) by age at survey, including the young group (18-40 years), middle-aged group (41-60 years), and elderly group (>60 years). RESULTS: Of the 1,664 respondents with MPNs, 349 (21.0%) were young including 244 (69.9%) with ET, 34 (9.7%) with PV, and 71 (20.3%) with MF. In multivariate analyses, the young groups with ET and MF were associated with the lowest MPN-10 scores among the 3 age groups; those with MF, highest proportion of reporting negative impact of disease and therapy on their daily life and work. The young groups with MPNs had the highest physical component summary scores but the lowest mental component summary scores in those with ET. The young groups with MPNs were most concerned about fertility; those with ET, treatment-related adverse events and long-term efficacy of treatment. CONCLUSIONS: We concluded that young adults with MPNs have different PROs compared with middle-aged and elderly patients.

Unrelated umbilical cord blood can improve the prognosis of haploidentical hematopoietic stem cell transplantation.

BACKGROUND: Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is widely used as a curative treatment strategy for most types of hematological diseases. However, strategies for enhancing the graft versus leukemia (GVL) effect without aggravating the graft versus host disease (GVHD) effect are still being pursued. METHODS: A retrospective cohort study was performed to compare the outcomes between combined unrelated umbilical cord blood (UCB-haplo HSCT) and haplo HSCT. RESULTS: The results showed that neither acute GVHD (aGVHD) nor chronic GVHD (cGVHD) was increased in the UCB-haplo HSCT group, and the engraftment and infection rates were similar between the two groups. However, overall survival and progression-free survival were significantly improved, while transplantation-related mortality and relapse were significantly decreased in the UCB-haplo HSCT group by both univariate and multivariate analyses. CONCLUSION: Our results indicated that the addition of a UCB unit could improve the prognosis of haplo-HSCT and enhance the GVL effect without increasing the incidence of GVHD. TRIAL REGISTRATION: The cohort study was retrospectively registered at https://www.chictr.org.cn as ChiCTR2100046681.

Analysis of microRNA expression profiles in exosomes derived from acute myeloid leukemia by p62 knockdown and effect on angiogenesis.

Objectives: In this study, we aimed to investigate the effect of p62 on angiogenesis and microRNA (miRNA) expression profiles in acute myeloid leukemia (AML) exosomes. Methods: An Exiqon v19.0 microRNA MicroArray was used to profile miRNAs in exosomes derived from parental and p62-knockdown U937 cells. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to predict the biological functions and potential mechanisms of differentially expressed miRNAs in AML exosomes. Endothelial cell tube formation assays using human umbilical vein endothelial cells (HUVECs) were performed to investigate the effect of AML exosomes on angiogenesis. Results: We demonstrated that 2,080 miRNAs were expressed in exosomes derived from our cultured cell samples, of which 215 and 208 miRNAs were upregulated and downregulated, respectively, in p62-knockdown U937 cells (fold change ≥ 2, P < 0.05). GO analysis indicated that miRNAs were most enriched in the intercellular pathways. Biological process analysis revealed that 1460 biological processes were associated with downregulated transcripts, including 19 pathways related to vesicles, and 1,515 pathways were upregulated, including 8 pathways related to vesicles. Molecular function analysis indicated that protein binding, transcription regulator activity, and DNA-binding transcription factor activity were enriched (P < 0.05). Pathway analysis indicated that 84 pathways corresponded to upregulated transcripts, and 55 pathways corresponded to downregulated transcripts (P < 0.05). We also found that exosomes derived from U937 cells promoted angiogenesis in HUVECs. Conclusions: Our data suggest that exosomal miRNAs may play important roles in the pathogenesis of AML, which may be treated by p62 knockdown with exosomal miRNAs to inhibit angiogenesis.

Expression of PD-L1 on regulatory B cells in patients with acute myeloid leukaemia and its effect on prognosis.

Programmed death-ligand 1 (PD-L1) is involved in immunosuppression in variety of tumours. Regulatory B cells (Bregs) are critical immune regulatory cells, and it has been demonstrated that the number of regulatory B cells in patients with acute myeloid leukaemia (AML) is much higher than that in healthy donors (HDs), which is linked to a poor prognosis. This study aimed to determine whether increased expression of PD-L1, including in Bregs, is associated with a worse prognosis in individuals with AML. The proportion of Bregs, PD-L1 expression in Bregs and PD-1 expression in T cells were determined using flow cytometry using patient samples from 21 newly diagnosed AML patients at different stages of treatment and 25 HDs. We confirmed PD-L1 expression in Bregs, and PD-1 expression in CD3+ CD4+ T cells in bone marrow and peripheral blood samples from AML patients was higher than that in samples from HDs. The complete remission (CR) and progression-free survival (PFS) of Bregs with high PD-L1 expression were significantly decreased following induction chemotherapy. PD-L1 expression is indeed increased in Bregs from individuals with AML, and high PD-L1 expression is related to a poor prognosis.

Selinexor plus low-dose dexamethasone in Chinese patients with relapsed/refractory multiple myeloma previously treated with an immunomodulatory agent and a proteasome inhibitor (MARCH): a phase II, single-arm study.

BACKGROUND: Selinexor 80 mg combined with low-dose dexamethasone (Sd) demonstrated significant clinical benefit in patients with relapsed/refractory multiple myeloma (RRMM) who had disease refractory to a proteasome inhibitor (PI), an immunomodulator (IMiD), and an anti-CD38 monoclonal antibody based on a global phase II STORM study. The present study, MARCH, addresses China regulatory needs to further validate the data from STORM in Chinese patients with RRMM. METHODS: The MARCH study was conducted at 17 sites in China, where eligible Chinese RRMM patients who had disease refractory to PI and IMiD were enrolled. Selinexor 80 mg combined with dexamethasone 20 mg was administered orally on day 1 and day 3 of each week in 4-week cycles. The primary endpoint was the overall response rate (ORR) per an independent review committee, with the null hypothesis of ≤15%. Patients who received at least 1 dose of study treatment were included in the safety population. The pharmacokinetic (PK) profile was characterized by parameter and ethnicity sensitivity analyses. RESULTS: A total of 82 patients with RRMM were enrolled in the study, with a median age of 60 years. Of the 82 patients, 55 patients (67.1%) had high-risk cytogenetic abnormalities, defined as one or more of del 17p13, t(4;14), t(14;16), or 1q amplification identified by fluorescence in situ hybridization (FISH); 18 patients (22.0%) had abnormal renal function. Enrolled patients were heavily pre-treated with a median prior regimen number of 5. All 82 patients (100%) were refractory to both PI and IMiD, including 20 patients (24.4%) categorized as triple-class refractory population (refractory to PI, IMiD, and daratumumab). Ten patients (12.2%) had undergone CAR-T therapy. ORR was 29.3% (95% CI 19.7, 40.4) with a median DOR of 4.7 months. The median PFS and OS were 3.7 and 13.2 months, respectively. ORR was 25.0% (95% CI 8.7, 49.1) in the triple-class refractory population. Efficacy was consistent across various subgroups. The most frequent grade 3/4 adverse events (AEs) included anemia (57.3%), thrombocytopenia (51.2%), lymphopenia (42.7%), neutropenia (40.2%), hyponatremia (29.3%), and lung infection (26.8%). Serious AEs were reported in 54.9% of patients. No significant drug accumulation was shown following multiple administrations. No human PK ethnicity difference was identified between Chinese and western patients. CONCLUSIONS: With an encouraging ORR, the MARCH study has demonstrated that selinexor combined with low-dose dexamethasone (Sd) delivers meaningful clinical benefit to Chinese patients with RRMM, including triple-class refractory patients. AEs were expected and manageable with supportive care and dose modification. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03944057 (May 09, 2019); Chinadrugtrials.org.cn , CTR20190858 (June 05, 2019).

Efficacy and safety of GLS-010 (zimberelimab) in patients with relapsed or refractory classical Hodgkin lymphoma: A multicenter, single-arm, phase II study.

BACKGROUND: GLS-010 (zimberelimab) is a novel, fully human, anti-programmed death-1 monoclonal antibody that shows promising efficacy and safety in advanced solid tumors. This trial aimed to evaluate the efficacy and safety of GLS-010 (zimberelimab) in Chinese patients with relapsed or refractory classical Hodgkin lymphoma (r/r-cHL). METHODS: This phase II, single-arm, open-label, multicenter clinical trial was conducted at 24 centers in China and enrolled patients with r/r-cHL after two or more lines of therapy. The patients were administered intravenous GLS-010 (zimberelimab) (240 mg, once every 2 weeks) until progression, death, unacceptable toxicity, or consent withdrawal. The primary end-point was the objective response rate assessed by an independent radiology review committee (IRC). This study was registered (NCT03655483). RESULTS: Eighty-five patients were enrolled between August 2018 and August 2019. The median follow-up was 15.8 months. Seventy-seven patients (90.6%; 95% confidence interval [CI] 82.3-95.9) had an IRC-assessed objective response. The complete response rate was 32.9% (n = 28). The 12-month progression-free survival and overall survival rates were 78% (95% CI 67.5-85.6) and 99% (95% CI 91.9-99.8), respectively. Treatment-related adverse events (TRAEs) were observed in 92.9% of participants. Grade III or IV TRAEs occurred in 24 (28.2%) of the 85 participants. The most common grade III or IV TRAEs were abnormal hepatic function (5.9%), hyperuricemia (4.7%), decreased neutrophil count (3.5%), and increased weight (3.5%). Only one grade V AE, gastrointestinal infection, occurred. CONCLUSIONS: GLS-010 (zimberelimab) appears to be effective and safe for the treatment of Chinese patients with r/r-cHL. Long-term follow-up is required to confirm these clinical benefits.

CDC45 modulates MCM7 expression and inhibits cell proliferation by suppressing the PI3K/AKT pathway in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogenous hematologic disease that has a poor prognosis. This study aimed to identify new targets for the diagnosis and treatment of AML. The GSE65409 and GSE90062 were selected from the AML database of the Gene Expression Omnibus and compared using the GEO2R tool to identify differentially expressed genes (DEGs). The Database for Annotation, Visualization, and Integrated Discovery was used to perform gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses of the DEGs. Protein-protein interactions were visualized using the Search Tool for the Retrieval of Interacting Genes, which identified two potential hub genes that encode CDC45 and MCM7. Relative to AML specimens, normal specimens had higher expression levels of CDC45 and MCM7 based on the Gene Expression Omnibus and The Cancer Genome Atlas databases. Furthermore, Pearson's correlation analysis revealed a significant relationship between CDC45 and MCM7. High expression of CDC45 was positively correlated with complete remission and negatively correlated with white blood cell count, hemoglobin concentration, platelet count, and bone marrow blasts. Moreover, high expression of MCM7 was negatively correlated with white blood cell count, hemoglobin concentration, platelet count, bone marrow blasts, and unfavorable cytogenetics. Overexpression of CDC45 increased the expressions of CDC45 and MCM7, while overexpression of MCM7 increased the expression of MCM7 but not CDC45. Overexpression of CDC45 or MCM7 led to impaired AML cell proliferation and blockage at the G1/S phase transition. Overexpression of CDC45 or MCM7 also attenuated the phosphorylation of PI3K, AKT, and mTOR, while simultaneous down-regulation of MCM7 expression abolished the effects of CDC45 overexpression. These findings suggest a functional relationship between CDC45 and MCM7, which might have use in the diagnosis and treatment of AML.

A concise prognostic score system for diffuse large B-cell lymphoma: a retrospective study with long-term follow-up.

Aim: To identify risk factors and establish a concise prognostic scoring system in patients with diffuse large B-cell lymphoma (DLBCL). Methods: A total of 131 DLBCL patients were enrolled with long-term follow-up who were treated in Shengjing Hospital of the China Medical University. The relationship between clinical parameters and outcomes was analyzed. Results: Multivariate analysis showed that patient age, BMI, CA125 and rituximab application were independent risk factors. Thereafter, a concise scoring system was established, and the new system could identify high-risk patients (p < 0.0001). The patients were divided into three groups: low-risk, medium-risk and high-risk groups. There were significant differences among different groups on overall survival and progression-free survival by log-rank test (p < 0.05). Conclusion: Old age, low BMI, high CA125 and no rituximab application were independent risk factors for DLBCL. The new established prognostic score system, which includes all the risk factors, could identify high-risk patients.

Lay abstract Diffuse large B-cell lymphoma (DLBCL) is the most common type of B-cell lymphoma. Different clinical performance and treatment options lead to different outcomes. Identifying factors that indicate poor prognosis is helpful for clinicians to plan a suitable treatment regimen. Therefore, it is important to establish a concise prognostic scoring system to identify high-risk DLBCL patients. This retrospective study analyzed 131 DLBCL patients with long-term follow-up with R-CHOP or E-CHOP therapy regimen. The result showed that patients' age, BMI, CA125 and chemotherapy regimens with or without rituximab were independent risk factors. Thereafter, we established a concise scoring system, which scored each risk factor including old age, low BMI, high CA125 and no rituximab application as 1 point each. Definition of low-risk (0­1 point), medium-risk (2 points) and high-risk (3­4 points) groups indicated significant differences in prognosis.

HLA-E Binding Peptide as a Potential Therapeutic Candidate for High-Risk Multiple Myeloma.

Human leukocyte antigen-E (HLA-E) has been putatively associated with the pathogenesis of multiple myeloma (MM). Our study first showed that HLA-E was differentially expressed on MM and normal plasma cells (39.27 ± 27.01 and 11.28 ± 0.79, respectively). Based on the median value of HLA-E expression, we further stratified MM patients into high and low-expression groups, and then found high expression of HLA-E was correlated with advanced ISS stage (p = 0.025) and high-risk cytogenetics risk stratification (p = 0.000) by the Pearson Chi-square test, suggesting that HLA-E could be considered as a biomarker for high-risk MM. Furthermore, peptide 3 (P3) from our previous study was confirmed to possess a high affinity to HLA-E positive MM cells. Taken together, HLA-E could be considered as a new marker and candidate treatment target for MM, while peptide P3 may act as a potential treatment choice for targeting MM cells.

Variables associated with patient-reported outcomes in patients with myeloproliferative neoplasms.

We explored variables associated with patient-reported outcomes (PROs) including symptom burden, impact on daily life and work, obstacles during therapy, satisfaction level with therapy, and health-related quality of life in 1500 respondents with myeloproliferative neoplasms (MPNs) including essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF) in a multicenter, cross-sectional study across China, a representative of the developing countries. In multivariate analyses, urban household registration and higher education level were significantly-associated with no symptoms at diagnosis in respondents with ET or MF. CALR mutation was significantly-associated with lower MPN-10 scores in respondents with MF. Higher MPN-10 scores were significantly-associated with negative impact on daily life and work as well as lower satisfaction level in respondents with ET, PV and MF. Receiving ruxolitinib was significantly-associated with high satisfaction and satisfaction in respondents with MF. In addition, other demographics and clinical variables were also impacting PROs.

FBN1 promotes DLBCL cell migration by activating the Wnt/ß-catenin signaling pathway and regulating TIMP1.

The heterogeneity of diffuse large B-cell lymphoma (DLBCL) acts as a main barrier to identify the genetic basis of the disease and the choice of treatment. Differentially expressed genes (DEGs) from three mRNA expression profile datasets were screened using GEO2R, and bioinformatics analysis was performed on the DEGs. A total of six upregulated and 13 downregulated DEGs were identified. Among these, two hub genes with a high degree of correlation were selected. FBN1 and TIMP1 were identified via STRING analysis and validated by GEPIA. FBN1 and TIMP1 were highly expressed in DLBCL tissues. FBN1 expression was significantly higher in patients of the Ann Arbor stage group (III-IV), with higher IPI score (3-5), and in the non-GCB group. Patients with high TIMP1 expression were more frequently associated with B symptoms, Ann Arbor stage (III-IV), higher IPI score (3-5) and were in the non-GCB group. Furthermore, FBN1 siRNA decreased FBN1 and TIMP1 expression and downregulation of TIMP1 attenuated TIMP1 expression but not of FBN1. Migration of DLBCL cells reduced when treated with either FBN1 or TIMP1 siRNA. Moreover, FBN1 or TIMP1 siRNA decreased the expression of Wnt target genes. Simultaneous overexpression of TIMP1 resulted in an increase in these proteins. This confirmed that both FBN1 and TIMP1 were positively associated with DLBCL progression. Further analysis revealed that FBN1/TIMP1 interaction could improve DLBCL cell migration and regulate the Wnt signaling pathway. Although the underlying mechanisms regarding the interaction between FBN1 and TIMP1 requires further clarification, they might be potential therapeutic targets for DLBCL therapy.

Effect of the Up-Regulation of Circular RNA Hsa_circ_0069767 Derived from C-KIT on the Biological Behavior of Multiple Myeloma Cells.

PURPOSE: Multiple myeloma (MM) is an incurable disease. This study focused on the expression of circular RNA circ_0069767 in MM and its influence on prognosis, in order to provide a potential target. PATIENTS AND METHODS: Totally 66 MM patients participated in this research. Using RT-PCR method to determine the expression level of circ_0069767 in 66 sorted samples from multiple myeloma patients and 21 normal control bone marrow samples, Kaplan-Meier was applied for survival analysis. We constructed stable over-expressing circ_0069767 and silenced circ_0069767 cell lines and used MTS experiment to detect cell viability, transwell experiment to detect cell migration and invasion ability and flow cytometry to detect cell apoptosis. Dual luciferase experiment, qRT-PCR experiment and Western blot were used to explore miRNA and downstream genes. RESULTS: The expression of circ_0069767 in MM was significantly higher than that of the normal control group. Patients with high expression of circ_0069767 had longer PFS and OS. Cell function experiments showed that overexpression of circ_0069767 in MM cells led to decreased proliferation, migration and invasion, but increased apoptosis; meanwhile, knockdown of circ_0069767 caused opposite biological behaviors. Circ_0069767 by sponging miR-636 in MM cells regulates the expression of K-RAS while the K-RAS gene remained unmutated. CONCLUSION: Circ_0069767 plays an antitumor role and its expression can be used as a reliable prognostic indicator for MM patients.

Designing high affinity target-binding peptides to HLA-E: a key membrane antigen of multiple myeloma.

Multiple myeloma (MM) is a plasma cell malignancy that is currently incurable. Finding new targets and designing drugs are crucial for the treatment of MM. The two datasets (GSE6691 and GSE39754) are used to screen highly expressed antigen on MM cells. HLA-E was an ideal target for it was a hub gene, and also located in one of the key clusters. Highly expression of HLA-E mRNA on MM cells was also confirmed by real-time qPCR testing the MM patients' samples in Shengjing hospital. Crystal structure of HLA-E was obtained from Protein Data Bank (PDB ID: 3CDG) which was used to design targeting peptides with Molecular Operating Environment software. By analyzing interaction between CD94/NKG2A and HLA-E, a peptide with twelve amino acids was screened as a model peptide. Peptides library was constructed by randomly replaced non-key amino acid. Peptide-protein docking method was used to identify high affinity peptides. PEPTIDE 1-3 and model peptide were synthesized and identified the affinity to HLA-E by flow cytometer and confocal laser microscopy. At last, PEPTIDE3 (NALDEYCEDKNR) was found with the highest affinity. Taking all, HLA-E is a new treatment target, and PEPTIDE 3 is an ideal high affinity target-binding peptide candidate.