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| 1 | Clinical characteristics and survival of patients with IgD multiple myeloma显示文摘MM(multiple myeloma)accounts for about 10%of hematological malignancies and 1%of cancer.IgD myeloma is a rare type of MM.It was reported that IgD type accounts for about 1%to 2%of all patients with MM abroad,while 3%to 8.9%in domestic cases.^(1) This immunoglobulin protein was first discovered by Dr.Rowe and Fahey in 1965.^(2) Half of a century had passed,the management of IgD MM remains a challenging field. | Yi Li Zhen Cai | 2021 | Blood Science2021，3，2： | 3 |
| 2 | PD-L1:expression regulation显示文摘Programmed death-ligand 1(PD-L1),expressed on the surface of tumor cells,can bind to programmed cell death-1(PD-1)on T cells.The interaction of PD-1 and PD-L1 can inhibit T-cell responses by decreasing T-cell activity and accelerating their apoptosis.Various cancers express high levels of PD-L1 and exploit PD-L1/PD-1 signaling to evade T-cell immunity,and immunotherapies targeting the PD-1/PD-L1 axis have been shown to exert remarkable anti-tumor effects;however,not all tumor patients benefit from these therapies.Therefore,study of the mechanisms regulating PD-L1 expression are imperative.In this review,we explore regulation of PD-L1 expression in the contexts of gene transcription,signaling pathways,histone modification and remodeling,microRNAs,long noncoding RNAs,and post-translational modification.Current developments in studies of agents that block PD-L1 and correlations between immunotherapies targeting PD-1/PD-L1 and PD-L1 expression are also summarized.Our review will assist in understanding of PD-L1 expression regulation and discusses the implications of reported findings in cancer diagnosis and immunotherapy. | Yu-Jie Zhou Guoli Li Jiyin Wang Mengyuan Liu Zihan Wang Yu Song Xulong Zhang Xi Wang | 2023 | Blood Science2023，5，2： | 3 |
| 3 | Macrophages in leukemia microenvironment显示文摘Macrophages,the important component of tissue microenvironment,play important roles in both physiological and pathological processes,including tumor and leukemia.Tumor-associated macrophages are involved in tumor proliferation,angiogenesis,invasion,metastasis,and chemotherapy resistance.In leukemia,macrophages are educated by leukemia microenvironment to obtain specific activated phenotype and participate in leukemia progression.Recent studies have shown that accumulation of macrophages in leukemia patients or mouse model is correlated with poor prognosis.Hence,increasing attentions have been paid to study the characteristics of them and to develop novel therapeutic strategies targeting macrophages against leukemia.In this article,we summarize recent development of macrophages in leukemia microenvironment. | Lina Wang Guoguang Zheng | 2019 | Blood Science2019，1，1： | 2 |
| 4 | DDIT4 mediates the proliferation-promotive effect of IL-34 in human monocytic leukemia cells显示文摘Interleukin 34(IL-34)is a cytokine that shares the receptor with colony-stimulating factor 1(CSF-1).IL-34 is involved in a broad range of pathologic processes including cancer.We previously demonstrated that IL-34 promoted the proliferation and colony formation of human acute monocytic leukemia(AMoL)cells.However,the mechanism has not been elucidated.Here,by analyzing the gene profiles of Molm13 and THP1 cells overexpressing IL-34(Molm13-IL-34 and THP1-IL-34),upregulation of the DNA damageinducible transcript 4(DDIT4)was detected in both series.Knockdown of DDIT4 effectively inhibited the proliferation,promoted apoptosis and colony formation in Molm13-IL-34 and THP1-IL-34 cells.Our results suggest that DDIT4 mediates the proliferationpromotive effect of IL-34 whereas does not mediate the promotive effect of IL-34 on colony formation in AMoL cells. | Xiaoqian Lv Yuting Hu Lina Wang Dongyue Zhang Hao Wang Yibo Dai Xiaoxi Cui Guoguang Zheng | 2021 | Blood Science2021，3，2： | 2 |
| 5 | Risk factors associated with hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation显示文摘Hemorrhagic cystitis(HC)is a common complication of allogeneic hematopoietic stem cell transplantation(HSCT).The incidence is about 7%to 68%,and some patients have to suffer a long period of frequent,urgent,and painful urination,which brings great pain.This study aimed to analyze risk factors of HC and its effect on patient survival.We collected the medical records of 859 patients who underwent HSCT at our hospital between August 2016 and August 2020.Patients with and without HC were matched using propensity score matching at a 1:1 ratio based on sex,age,and diagnosis,and logistic regression analyses were used to identify factors associated with HC.We used Kaplan–Meier curves to analyze the survival rates of patients in the HC and non-HC groups.We also analyzed the relationship between BK viral load and the occurrence of HC using receiver operating characteristic curve(ROC)analysis.After propensity score matching,there were 131 patients each in the HC and non-HC groups.In the HC group,89 patients(67.9%)had mild HC(stage II°)and 43(32.1%)had severe HC(stage III–IV).The median interval between stem cell transplantation and HC development was 31(3–244)days.Univariate analysis indicated that donor age,hematopoietic stem cell source,HLA,acute graft-versus-host disease,busulfan,anti-thymocyte globulin(ATG),total body irradiation,cytomegalovirus(CMV)(urine),and BK polyomavirus(BKV)(urine)were significantly associated with HC.ATG,CMV(urine),and BKV(urine)were independent risk factors for HC based on the multivariate analysis.The Kaplan–Meier survival analysis showed no significant difference between the HC and non-HC groups(P=0.14).The 1-and 2-year survival rates in the HC group were 78.4%and 69.6%,respectively,and the corresponding rates in the non-HC group were 84.4%and 80.7%,respectively.ROC analysis indicated that a urine BKV load of 1×10^(7) copies/mL was able to stratify the risk of HC.In conclusion,when the BKV load is>1×10^(7),we needtobe aware of the potential for the development of HC. | Biao Shen Yueshen Ma Haixiao Zhang Mingyang Wang Jia Liu Jiaxin Cao Wenwen Guo Dan Feng Donglin Yang Rongli Zhang Xin Chen Qiaoling Ma Weihua Zhai Sizhou Feng Mingzhe Han Aiming Pang Erlie Jiang 无 | 2022 | Blood Science2022，4，2： | 2 |
| 6 | Carbon dots for the treatment of cancer-related anemia显示文摘Erythropoiesis is the process in which hematopoietic stem cells(HSCs)differentiate,proliferate,and eventually form mature red blood cells.1 The early phase of erythropoiesis involves HSC commitment to erythroid progenitors includ-ing burst-forming unit-erythroid(BFU-E)and colony forming unit-erythroid(CFU-E). | Xu Han Peng Ji | 2022 | Blood Science2022，4，3： | 1 |
| 7 | LILRB4, an immune checkpoint on myeloid cells显示文摘Leukocyte immunoglobulin-like receptor B4(LILRB4)is an inhibitory receptor in the LILR family mainly expressed on normal and malignant human cells of myeloid origin.By binding to ligands,LILRB4 is activated and subsequently recruits adaptors to cytoplasmic immunoreceptor tyrosine inhibitory motifs to initiate different signaling cascades,thus playing an important role in physiological and pathological conditions,including autoimmune diseases,microbial infections,and cancers.In normal myeloid cells,LILRB4 regulates intrinsic cell activation and differentiation.In disease-associated or malignant myeloid cells,LILRB4 is significantly correlated with disease severity or patient survival and suppresses T cells,thereby participating in the pathogenesis of various diseases.In summary,LILRB4 functions as an immune checkpoint on myeloid cells and may be a promising therapeutic target for various human immune diseases,especially for cancer immunotherapy. | Ting Yang Yixin Qian Xiaoting Liang Jianbo Wu Ming Zou Mi Deng | 2022 | Blood Science2022，4，2： | 1 |
| 8 | Treatment of STAT5b-RARA positive acute promyelocytic leukemia by Venetoclax combining with homoharringtonine, cytarabine: A case report and literature review显示文摘Introduction:Acute promyelocytic leukemia(APL)is mostly due to the chromosome translocation t(15;17)(q22;q12),leading to the formation of PML-RARA fusion protein.Some patients carried rare translocation involving RARA gene,who were called variant APL caused by RAR family(RARA,RARB,and RARG)and partner genes.STAT5b-RARA was a rare type of molecular genetic abnormality with unfavorable prognosis which have been reported in only 18 cases in variant APL.Knowledge of STAT5b-RARA(+)APL treatment is still limited.Case report:We presented a 38-year-old female variant APL case,who was STAT5b-RARA positive detected by reverse transcription polymerase chain reaction.The patient failed to respond after four-drug combined induction chemotherapy:idarubicin,cytarabine,all trans retinoic acid,and arsenic trioxide(As 2 O 3).Then,the patient was re-induced with azacytidine,but still failed to achieve complete remission(CR).Next,she was treated with Venetoclax combining with homoharringtonine and cytarabine as the salvage therapy and achieved CR.Later,the patient received hematopoietic stem cell transplantation after 4 cycles of consolidation therapy.Conclusion:Venetoclax combining with homoharringtonine and cytarabine has been used as the salvage therapy in the STAT5b-RARA positive APL successfully. | Guangji Zhang Yang Song Li Wan Kaiqi Liu Shaowei Qiu Jianxiang Wang Yingchang Mi | 2022 | Blood Science2022，4，2： | 1 |
| 9 | Epigenetic regulation of hematopoietic stem cell homeostasis显示文摘As one of the best characterized adult stem cells,hematopoietic stem cell(HSC)homeostasis is of great importance to hematopoiesis and immunity due to HSC’s abilities of self-renewal and multi-lineage differentiation into functional blood cells.However,excessive self-renewal of HSCs can lead to severe hematopoietic malignancies like leukemia,whereas deficient selfrenewal of HSCs may result in HSC exhaustion and eventually apoptosis of specialized cells,giving rise to abnormalities such as immunodeficiency or anemia.How HSC homeostasis is maintained has been studied for decades and regulatory factors can be generally categorized into two classes:genetic factors and epigenetic factors.Although genetic factors such as signaling pathways or transcription factors have been well explored,recent studies have emerged the indispensable roles of epigenetic factors.In this review,we have summarized regulatory mechanisms of HSC homeostasis by epigenetic factors,including DNA methylation,histone modification,chromatin remodeling,non-coding RNAs,and RNA modification,which will facilitate applications such as HSC ex vivo expansion and exploration of novel therapeutic approaches for many hematological diseases. | Penglei Jiang Hui Wang Jiachen Zheng Yingli Han He Huang Pengxu Qian | 2019 | Blood Science2019，1，1： | 1 |
| 10 | Transcriptional addiction in mixed lineage leukemia: new avenues for target therapies显示文摘Mixed lineage leukemia(MLL)is an aggressive and refractory blood cancer that predominantly occurs in pediatric patients and is often associated with poor prognosis and dismal outcomes.Thus far,no effective target therapy for the treatment of MLL leukemia is available.MLL leukemia is caused by the rearrangement of MLL genes at 11q23,which generates various MLL chimeric proteins that promote leukemogenesis through transcriptional misregulation of MLL target genes.Biochemical studies on MLL chimeras have identified that the most common partners exist in the superelongation complex(SEC)and DOT1L complex,which activate or sustain MLL target gene expression through processive transcription elongation.The results of these studies indicate a transcription-related mechanism for MLL leukemogenesis and maintenance.In this study,we first review the history of MLL leukemia and its related clinical features.Then,we discuss the biological functions of MLL and MLL chimeras,significant cooperating events,and transcriptional addiction mechanisms in MLL leukemia with an emphasis on potential and rational therapy development.Collectively,we believe that targeting the transcriptional addiction mediated by SEC and the DOT1L complex will provide new avenues for target therapies in MLL leukemia and serve as a novel paradigm for targeting transcriptional addiction in other cancers. | Ruijing Xiao Honghong Wang Kaiwei Liang | 2019 | Blood Science2019，1，1： | 1 |
| 11 | Erythroblast island macrophages: recent discovery and future perspectives显示文摘Erythroblastic island(EBI),composed of a central macrophage surrounded by developing erythroid cells,is a structure found in hematopoietic tissues such as fetal liver and bone marrow.It is the first described hematopoietic niche that predominantly supports erythropoiesis.Although it is well accepted that EBIs and EBI macrophage play important roles during erythropoiesis,the mechanisms by which they support erythropoiesis remain largely unclear due to our inability to identify and isolate EBI macrophages.Earlier efforts to identify surface markers for EBI macrophages have focused on the adhesion molecules which are involved in macrophage’s interaction with erythroblasts.These include EMP,Vcam1,CD169,CD163,and aV integrin.Findings from these earlier studies suggested that combination of Vcam1,CD169,and mouse macrophage surface marker F4/80 can be used to define mouse EBI macrophage.We found that not all F4/80+Vcam1+CD169+macrophages are EBI macrophages.Instead,we discovered that EBI macrophages are characterized by the expression of Epor in both mouse and man.RNA-seq analyses of the newly identified EBI macrophages revealed that EBI macrophages have involved specialized function in supporting erythropoiesis.Our findings provide foundation for future studies.Here we will review current knowledge of EBI macrophages and discuss future perspectives. | Wei Li Yaomei Wang Lixiang Chen Xiuli An | 2019 | Blood Science2019，1，1： | 1 |
| 12 | Quickly attainable and highly engrafting hematopoietic stem cells显示文摘There are three clinically used sources of hematopoietic stem cells(HSC)and hematopoietic progenitor cells(HPC)for hematopoietic cell transplantation(HCT):bone marrow(BM),umbilical cord blood(CB),and cytokine-induced mobilized peripheral blood(mPB)cells.1–5 Each source of clinically used cells has its advantages and disadvantages.Of these,mPB cells make up the majority of autologous and allogeneic HCT efforts worldwide.The advantage of mPB is that one can,in many cases,usually collect more than enough cells to ensure a rapid and longlasting donor graft,be it for autologous or allogeneic HCT.The“gold”standard for collection of mPB has been,and continues to be,the cells mobilized from the BM to peripheral blood by multiple additions of the cytokine granulocyte colony-stimulating factor(G-CSF)each day over a number of days.However,GCSF-induced mPB does not always yield enough cells for a graft,takes 4–5 days for optimal yield of HSC and HPC,and can entail leukocytapheresis efforts to obtain enough cells for a transplant.This requires the donor to be ready and willing for multiple days of G-CSF treatment.Moreover,there are patients who do not mobilize HSC and HPC well for a number of reasons,including low numbers of these cells inherent in the BM of the patient undergoing an autologous transplant—an example being patients with Fanconi anemia,under such conditions,one might attempt to use gene therapy on the mobilized cells to correct the Fanconi anemia gene defect.New,simple,and less timeconsuming efforts to mobilize HSC and HPC for clinical use would be advantageous.In this context,a recent article by Hoggatt et al.6 describes a new regimen combining two small molecules(GRO-beta and AMD3100)to quickly mobilize HSC and HPC in mice. | Hal E.Broxmeyer | 2019 | Blood Science2019，1，1： | 1 |
| 13 | Advances of adeno-associated virus applied in gene therapy to hemophilia from bench work to the clinical use显示文摘Hemophilia A and B are diseases caused by a single gene deficiency and are thus suitable for gene therapy.In recent clinical research,adeno-associated virus(AAV)was employed by several teams in the treatment of hemophilia A and B,and the outcomes were encouraging.In this review,we summarized the most recent research on the mechanism and application of AAV in the treatment of hemophilia,trying to analyze the advantages of AAV gene therapy and the main challenges in its clinical use.We also summarized the clinical trials involving hemophilia,especially those employing AAV gene therapy to treat hemophilia A and B,some of which have already been completed and some that are still ongoing.From the reports of the completed clinical trials,we tried to determine the correlations among AAV dose,AAV serotype,immune response,and gene expression time.Finally,taking into account the most recent studies investigating AAV capsid modification,transgene optimization,and AAV chaperones,we summarized the direction of basic research and clinical applications of AAV in the future. | Xiaolei Pei Mingzhe Han Lei Zhang | 2019 | Blood Science2019，1，2： | 1 |
| 14 | Machine learning algorithm as a prognostic tool for Epstein-Barr virus reactivation after haploidentical hematopoietic stem cell transplantation显示文摘Epstein-Barr virus(EBV)reactivation is one of the most important infections after hematopoietic stem cell transplantation(HSCT)using haplo-identical related donors(HID).We aimed to establish a comprehensive model with machine learning,which could predict EBV reactivation after HID HSCT with anti-thymocyte globulin(ATG)for graft-versus-host disease(GVHD)prophylaxis.We enrolled 470 consecutive acute leukemia patients,60%of them(n=282)randomly selected as a training cohort,the remaining 40%(n=188)as a validation cohort.The equation was as follows:Probability(EBV reactivation)=1/1+exp(−Y),where Y=0.0250×(age)–0.3614×(gender)+0.0668×(underlying disease)–0.6297×(disease status before HSCT)–0.0726×(disease risk index)–0.0118×(hematopoietic cell transplantation-specific comorbidity index[HCT-CI]score)+1.2037×(human leukocyte antigen disparity)+0.5347×(EBV serostatus)+0.1605×(conditioning regimen)–0.2270×(donor/recipient gender matched)+0.2304×(donor/recipient relation)–0.0170×(mononuclear cell counts in graft)+0.0395×(CD34+cell count in graft)–2.4510.The threshold of probability was 0.4623,which separated patients into low-and high-risk groups.The 1-year cumulative incidence of EBV reactivation in the low-and high-risk groups was 11.0%versus 24.5%(P<.001),10.7%versus 19.3%(P=.046),and 11.4%versus 31.6%(P=.001),respectively,in total,training and validation cohorts.The model could also predict relapse and survival after HID HSCT.We established a comprehensive model that could predict EBV reactivation in HID HSCT recipients using ATG for GVHD prophylaxis. | ShuangFan Hao-Yang Hong Xin-Yu Dong Lan-Ping Xu Xiao-Hui Zhang Yu Wang Chen-Hua Yan Huan Chen Yu-Hong Chen Wei Han Feng-Rong Wang Jing-Zhi Wanga Kai-Yan Liu Meng-Zhu Shen Xiao-Jun Huang Shen-Da Hong Xiao-Dong Mo | 2023 | Blood Science2023，5，1： | 1 |
| 15 | Dynamic regulation of GATA2 in fate determination in hematopoiesis: possible approach to hPSC-derived hematopoietic stem/ progenitor cells显示文摘GATA2,a principal member of the GATA family,plays important roles in the generation and maintenance of hematopoietic stem/progenitor cells.Among the three mRNA transcripts,the distal first exon of GATA2(IS exon)is specific for hematopoietic and neuronal cells.GATA2 mutants with abnormal expression are often present in acute myeloid leukemia-related familial diseases and myelodysplastic syndrome,indicating the crucial significance of GATA2 in the proper maintenance of blood system functions.This article offers an overview of the regulation dynamics and function of GATA2 in the generation,proliferation,and function of hematopoietic stem cells in both mouse and human models.We acknowledge the current progress in the cell fate determination mechanism by dynamic GATA2 expression.The gene modification approaches for inspecting the role of GATA2 in definitive hematopoiesis demonstrate the potential for acquiring hPSC-derived hematopoietic stem cells via manipulated GATA2 regulation. | Ya Zhou Bin Mao Yijin Chen Yuan Xue Bo Chen Yonggang Zhang Feng Ma | 2020 | Blood Science2020，2，1： | 1 |
| 16 | T cell metabolism in graft-versus-host disease显示文摘Graft-versus-host disease(GVHD)is a major source of morbidity and mortality following allogeneic hematopoietic stem cell transplant(allo-HSCT),one of the most effective approaches to treat hematopoietic malignancies.1 However,current prophylaxis regimens and treatments that reduce the detrimental effect of acute GVHD can be offset by increased incidence in opportunistic infections and relapse of the primary malignancy.2 In addition,the majority of the approaches that inhibit T cell responses are non-specific,resulting in the inhibition of both alloreactive T cells and protective T cells from the donor.Therefore,there is an increase in the demand to develop novel approaches that selectively target alloreactive T cells.One potential means to address this issue is to take advantage of the unique metabolic profile of activated T cells. | Yujing Zou Benny J.Chen | 2020 | Blood Science2020，2，1： | 1 |
| 17 | Immune targeted therapy for diffuse large B cell lymphoma显示文摘Diffuse large B-cell lymphoma(DLBCL),the most common subtype of non-Hodgkin lymphoma,is highly heterogeneous and invasive.Although the majority of DLBCL patients show a good response to rituximab plus cyclophosphamide,doxorubicin,vincristine,and prednisone treatment,approximately one-third of patients still have a poor prognosis.Many immune-targeted drugs,such as bispecific T-cell engagers and CAR T-cell therapy,have been proven effective for refractory and relapsed patients.This article reviews the progress of immune targeted therapy for DLBCL. | Yaxin Zheng Junqi Si Tian Yuan Sa Ding Chen Tian | 2021 | Blood Science2021，3，4： | 1 |
| 18 | Regulation of megakaryopoiesis by bone marrow macrophage polarization显示文摘Immune thrombocytopenia(ITP)is an autoimmune disorder characterized by increased bleeding tendency and thrombocytopenia.The main mechanisms include the loss of immune tolerance,accelerated platelet destruction,impaired bone marrow(BM)microenvironment,and decreased platelet production.1–5 The processes of megakaryocytopoiesis and thrombocytopoiesis occur within a complex BM microenvironment.Macrophages(MFs)are crucial regulators of normal hematopoiesis in the BM microenvironment,whereas very few studies focus on the effect of BM MFs on megakaryopoiesis,especially the MF polarization subsets in thrombocytopenic disease.Prolonged thrombocytopenia(PT)after hematopoietic stem cell transplantation is a strong risk factor for transplantation-related morbidity and mortality,and no standard treatment guideline exists.Meanwhile,PT,characterized by dysfunctional megakaryocyte(MK)maturation and thrombocytopenia,not only provides a paradigm for understanding the relationship between MK development and BM microenvironment but also an ideal disease model for studying thrombocytopenia。 | Ming Hou | 2021 | Blood Science2021，3，4： | 1 |
| 19 | HSP70 and FLT3-ITD: Targeting chaperone systemto overcome drug resistance显示文摘Acute myeloid leukemia (AML) is an aggressive hematologicmalignancy characterized by the abnormal differentiation andrapid proliferation of hematopoietic cells. The causes of this typeof blood cancer are multiple, with approximately 30% of AMLpatients characterized by expression of the internal tandemduplication (ITD) of the Fms-like tyrosine kinase 3 (FLT3) gene.1Despite the availability of effective FLT3 inhibitors, alone orcombined with conventional chemotherapy, for the treatment ofFLT3-ITD AML, there is a risk of leukemia relapse due to drugresistance. Reasons for drug resistance include the evolution ofthe secondary mutations of FLT3 in response to drug treatmentand compensatory activation of survival signaling pathways.2Therefore, the discovery of new drug targets and noveltherapeutic strategies for FLT3-ITD-positive AML is imperativefor overcoming resistance to FLT3 inhibitors. | Jing Yang Ellen L.Weisberg | 2021 | Blood Science2021，3，4： | 1 |
| 20 | Abnormal bone marrow microenvironment: the “harbor” of acute lymphoblastic leukemia cells显示文摘Bone marrow(BM)microenvironment regulates and supports the production of blood cells which are necessary to maintain homeostasis.In analogy to normal hematopoiesis,leukemogenesis is originated from leukemic stem cells(LSCs)which gives rise to more differentiated malignant cells.Leukemia cells occupy BM niches and reconstruct them to support leukemogenesis.The abnormal BM niches are the main sanctuary of LSCs where they can evade chemotherapy-induced death and acquire drug resistance.In this review,we focus on the protective effects of BM niche cells on acute lymphoblastic leukemia cells. | Zehui Chen Yaxin Zheng Yaling Yang Junnan Kang M.James You Chen Tian | 2021 | Blood Science2021，3，2： | 1 |
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