PURPOSE:This study was designed to investigate the relationship between peripheral blood inflammatory markers and prognosis in MDS patients. METHODS:We conducted a study involving 183 MDS patients who were diagnosed at Taizhou Hospital of Zhejiang Province and Enze Hospital between January 2015 and December 2019. The end point of follow-up was September 2022. To minimize the impact of other confounding factors among the 110 included MDS patients, X-tile software was used to determine the optimal cutoff points for peripheral blood inflammation markers. Based on these cutoff points, the cohort of patients was divided into a high-risk group and a low-risk group. The OS in each group was analyzed by the Kaplan-Meier method, and univariate and multivariate Cox regression analyses were employed. RESULTS:The MDS patients included 73 men and 37 women with a median age of 72 years (32-92 years). The median OS was 28 months (1-83 months), 17 patients (15.45%) experienced conversion to AML, and 94 patients (85.45%) died during the follow-up period. The optimal cutoff points were ALC (1.2 × 109/L), AMC (0 × 109/L), CRP (6.1 mg/L), MLR (0.125), NLR (2.25) and PLR (71.4). Patients in the ALC (≤1.2 × 109/L, P = 0.017), MLR (>0.125, P = 0.01), PLR (>71.43, P = 0.044), and CRP (>6.1 mg/L, P < 0.0001) groups had shorter overall survival. The MLR (>0.125, P = 0.011) and CRP (>6.1 mg/L, P = 0.017) levels were related to poor prognosis. CONCLUSIONS:Elevated MLR and CRP levels may be independent indicators of poor prognosis in newly diagnosed MDS patients.

Early detection and accurate diagnosis of leukemia pose significant challenges due to the disease’s complexity and the need for minimally invasive methods. Acute myeloid leukemia (AML) accounts for most cases of adult leukemia, and our goal is to screen out some AML from adults. In this work, we introduce an AI-enhanced system designed to facilitate early screening and diagnosis of AML among adults. Our approach combines the infrared absorption spectra of serum measured with attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), which identifies distinctive molecular signatures in lyophilized serum, together with standard clinical blood biochemical test results. We developed a multi-modality spectral transformer network (MSTNetwork) to generate latent space feature vectors from these datasets. Subsequently, these vectors were assessed using a linear discriminant analysis (LDA) algorithm to estimate the likelihood of acute myeloid leukemia. By analyzing blood samples from leukemia patients and the negative control (including non-leukemia patients and healthy individuals), we achieved rapid and accurate prediction and identification of acute myeloid leukemia among adults. Compared to conventional methods relying solely on either FTIR spectra or biochemical indicators of blood, our multi-modality classification system demonstrated higher accuracy and sensitivity, ultimately achieving an accuracy of 98% and a sensitivity of 98%, improving the sensitivity by 12% (compared with using only biochemical indicators) or over 6% (compared with using only FTIR spectra). Our multi-modality classification system is also very robust as it gave much smaller standard deviations of the accuracy and sensitivity. Beyond improving early detection, this work also contributes to a more sustainable and intelligent healthcare sector.

Acute lysis pneumopathy (ALP) is a rare but fatal complication that can occur during induction chemotherapy for newly diagnosed acute myeloid leukaemia (AML). Currently, there is a paucity of large case reports detailing high-risk and poor prognostic factors associated with its occurrence. To provide evidence-based guidance on ALP, we conducted a retrospective analysis of 608 patients with newly diagnosed AML (non-M3), among whom 20 developed ALP during hydroxycarbamide (hydroxyurea) therapy and/or induction chemotherapy, resulting in an overall incidence rate of 3.3% (20/608) and a mortality rate of 35% (7/20). Multivariable logistic regression revealed that male (odds ratio [OR] 5.852, 95% confidence interval [CI]: 1.006-34.028, p = 0.049), elevated leucocyte counts (OR 1.125, 95% CI: 1.050-1.205, p = 0.001) and CBFβ::MYH11 fusion positivity (OR 13.821, 95% CI: 3.002-63.634, p = 0.001) were independent risk factors for the occurrence of ALP. Notably, CBFβ::MYH11 fusion positivity was associated with improved survival in ALP patients (p = 0.015). This study provides preliminary insights into the risk and prognostic factors of ALP.

BACKGROUND:The endothelial-to-hematopoietic transition (EHT) process during definitive hematopoiesis is highly conserved in vertebrates. Stage-specific expression of transposable elements (TEs) has been detected during zebrafish EHT and may promote hematopoietic stem cell (HSC) formation by activating inflammatory signaling. However, little is known about how TEs contribute to the EHT process in human and mouse. RESULTS:We reconstructed the single-cell EHT trajectories of human and mouse and resolved the dynamic expression patterns of TEs during EHT. Most TEs presented a transient co-upregulation pattern along the conserved EHT trajectories, coinciding with the temporal relaxation of epigenetic silencing systems. TE products can be sensed by multiple pattern recognition receptors, triggering inflammatory signaling to facilitate HSC emergence. Interestingly, we observed that hypoxia-related signals were enriched in cells with higher TE expression. Furthermore, we constructed the hematopoietic cis-regulatory network of accessible TEs and identified potential TE-derived enhancers that may boost the expression of specific EHT marker genes. CONCLUSIONS:Our study provides a systematic vision of how TEs are dynamically controlled to promote the hematopoietic fate decisions through transcriptional and cis-regulatory networks, and pre-train the immunity of nascent HSCs.

Morphological differentiation between myeloblasts and monoblasts is pivotal for the majority of acute myeloid leukemia (AML) diagnosis in clinical settings. Manual morphology-based classification of blasts encounters challenges due to the limited differentiation of these bone marrow cells (BMC) of early stages. Hence, the utilization of artificial intelligence is essential to assist in the classification of these cells. 4001 single-cell images of monoblasts and myeloblasts were collected from Taizhou Hospital to form the BMC-1 dataset. The main novelties and features of the proposed method are as follows: 1) A maximum connected domain extraction method grounded in the watershed algorithm is introduced to efficiently eliminate stained impurity cells from single cell images. 2) A dynamic focal loss is introduced to gradually focus on difficult-to-classify samples as the training progresses. 3) A dual-channel convolutional block attention network (DCCBANet) is introduced to enhance feature extraction. It employs attention mechanisms to focus on key features, utilizing ordinary convolution for local feature extraction, dilated convolution for global feature extraction, and a decreasing dilation rate sequence to preserve detailed information. A macro F1-score (macro_F) of 96.8% is achieved on the BMC-1 validation dataset. Additionally, the presence of multiple differentiation types of granulocytes pose difficulties in granulocytes distinction. To further validate the efficacy of our proposed method on multi-classification tasks, we collected 6626 granulocyte single-cell images from Taizhou Hospital. Augmenting the dataset with 2441 granulocyte single-cell images from the public dataset BM_cytomorphology addressed sample shortages, forming the BMC-2 dataset. We applied our model to the BMC-2 dataset for experiments and ultimately achieved a macro_F of 87.49%. Our proposed method effectively distinguishes monoblasts and myeloblasts and excels in the classification of granulocytes.

Abstract Autologous hematopoietic stem-cell transplantation (ASCT) is one of the most effective therapies for the treatment of multiple myeloma (MM). In this study, we explored factors influencing patients in selecting ASCT by analyzing population-based epidemiological data on patients’ sociodemographic and clinical variables. This multicenter study was conducted across 14 medical centers in Zhejiang Province in China. Patient survey was conducted via face-to-face interviews, telephone interviews, or online completion of questionnaire with patients’ informed consent. Patients were divided into transplantation (TR) and non-transplantation (non-TR) groups. The difference in education levels, occupational status, and annual income between the TR group and non-TR group was significant (P < 0.01). The main reasons that patients had chosen transplantation were "to delay recurrence, improve quality of life, prolong survival" and "trust the treatment provided by doctors", the main reason that patients had rejected transplantation was "worried about the physical condition”, followed by “risk of relapse”, “side effects” and “family burden”. In addition to discussing therapy with their primary physician, patients in TR group tended to obtain relevant information from other sources. Education levels, occupational status, and annual income were the main factors affecting transplantation therapy choice among patients with MM.

Background: Diffuse large B-cell lymphoma (DLBCL), which is considered to be the most common subtype of lymphoma, is an aggressive tumor. Necroptosis, a novel type of programmed cell death, plays a bidirectional role in tumors and participates in the tumor microenvironment to influence tumor development. Targeting necroptosis is an intriguing direction, whereas its role in DLBCL needs to be further discussed. Methods: We obtained 17 DLBCL-associated necroptosis-related genes by univariate cox regression screening. We clustered in GSE31312 depending on their expressions of these 17 genes and analyzed the differences in clinical characteristics between different clusters. To investigate the differences in prognosis across distinct clusters, the Kaplan-Meier method was utilized. The variations in the tumor immune microenvironment (TME) between distinct necroptosis-related clusters were investigated via "ESTIMATE", "Cibersort" and single-sample geneset enrichment analysis (ssGSEA). Finally, we constructed a 6-gene prognostic model by lasso-cox regression and subsequently integrated clinical features to construct a prognostic nomogram. Results: Our analysis indicated stable but distinct mechanism of action of necroptosis in DLBCL. Based on necroptosis-related genes and cluster-associated genes, we identified three groups of patients with significant differences in prognosis, TME, and chemotherapy drug sensitivity. Analysis of immune infiltration in the TME showed that cluster 1, which displayed the best prognosis, was significantly infiltrated by natural killer T cells, dendritic cells, CD8+ T cells, and M1 macrophages. Cluster 3 presented M2 macrophage infiltration and the worst prognosis. Importantly, the prognostic model successfully differentiated high-risk from low-risk patients, and could forecast the survival of DLBCL patients. And the constructed nomogram demonstrated a remarkable capacity to forecast the survival time of DLBCL patients after incorporating predictive clinical characteristics. Conclusion: The different patterns of necroptosis explain its role in regulating the immune microenvironment of DLBCL and the response to R-CHOP treatment. Systematic assessment of necroptosis patterns in patients with DLBCL will help us understand the characteristics of tumor microenvironment cell infiltration and aid in the development of tailored therapy regimens.

目的 探讨微小RNA(miR)-92a-3p对急性T淋巴细胞白血病(T-ALL)SupT1细胞增殖的影响及其机制.方法 将体外培养的SupT1细胞分为未转染组(正常培养)、阴性对照组(转染阴性对照)、模拟物组(转染miR-92a-3p模拟物)和抑制剂组(转染miR-92a-3p抑制剂),采用实时荧光定量PCR(RT-qPCR)检测SupT1细胞中miR-92a-3p表达水平,噻唑蓝(M T T)实验检测SupT1细胞增殖活力,流式细胞仪检测SupT1细胞周期分布情况,Western blot检测SupT1细胞中果蝇翅膀边缘出现缺口(NOTCH)信号通路相关蛋白NOTCH1、NOTCH配体Jagged1和效应分子Hes1蛋白表达情况,双荧光素酶报告基因(DLR)实验检测miR-92a-3p和NOTCH1的靶向关系.结果 与阴性对照组比较,模拟物组SupT1细胞中miR-92a-3p表达水平、G0/G1期细胞所占百分比明显升高,且细胞增殖活力和细胞在S期、G2/M期所占百分比及细胞中N O T C H1、Jagged1、Hes1蛋白表达水平均明显降低(P<0.05);而抑制剂组细胞各指标变化与模拟物组结果相反;阴性对照组与未转染组比较,各指标差异无统计学意义(P>0.05);DLR实验结果证实miR-92a-3p可与NOTCH1靶向结合.结论 miR-92a-3p可通过诱导细胞周期阻滞抑制SupT1细胞增殖,其作用机制可能与靶向调控NOTCH信号通路有关.

BackgroundMultiple myeloma (MM) is a malignant hematopoietic disease that is usually incurable. RNA-binding proteins (RBPs) are involved in the development of many tumors, but their prognostic significance has not been systematically described in MM. Here, we developed a prognostic signature based on eight RBP-related genes to distinguish MM cohorts with different prognoses.MethodAfter screening the differentially expressed RBPs, univariate Cox regression was performed to evaluate the prognostic relevance of each gene using The Cancer Genome Atlas (TCGA)-Multiple Myeloma Research Foundation (MMRF) dataset. Lasso and stepwise Cox regressions were used to establish a risk prediction model through the training set, and they were validated in three Gene Expression Omnibus (GEO) datasets. We developed a signature based on eight RBP-related genes, which could classify MM patients into high- and low-score groups. The predictive ability was evaluated using bioinformatics methods. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and gene set enrichment analyses were performed to identify potentially significant biological processes (BPs) in MM.ResultThe prognostic signature performed well in the TCGA-MMRF dataset. The signature includes eight hub genes: HNRNPC, RPLP2, SNRPB, EXOSC8, RARS2, MRPS31, ZC3H6, and DROSHA. Kaplan–Meier survival curves showed that the prognosis of the risk status showed significant differences. A nomogram was constructed with age; B2M, LDH, and ALB levels; and risk status as prognostic parameters. Receiver operating characteristic (ROC) curve, C-index, calibration analysis, and decision curve analysis (DCA) showed that the risk module and nomogram performed well in 1, 3, 5, and 7-year overall survival (OS). Functional analysis suggested that the spliceosome pathway may be a major pathway by which RBPs are involved in myeloma development. Moreover, our signature can improve on the R-International Staging System (ISS)/ISS scoring system (especially for stage II), which may have guiding significance for the future.ConclusionWe constructed and verified the 8-RBP signature, which can effectively predict the prognosis of myeloma patients, and suggested that RBPs are promising biomarkers for MM.

Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or <5 patients per year, p = 0.12) or age (≥60 or <60 years, p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count (>10 × 109/L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future.

Background: Diffuse large B-cell lymphoma (DLBCL) is a common aggressive B-cell non-Hodgkin lymphoma (B-NHL). While combined chemotherapy has improved the outcomes of DLBCL, it remains a highly detrimental disease. Pyroptosis, an inflammatory programmed cell death, is considered to have both tumor-promoting and tumor-suppressing effects. The role of pyroptosis in DLBCL has been gradually appreciated, but its value needs further investigation. Methods: We analyzed mutations and copy number variation (CNV) alterations of pyroptosis-related genes (PRGs) from The Cancer Genome Atlas (TCGA) cohort and evaluated the differences in expression in normal B cells and DLBCL patients in two Gene Expression Omnibus (GEO) datasets (GSE12195 and GSE56315). Based on the expression of 52 PRGs, we divided 421 DLBCL patients from the GSE31312 dataset into distinct clusters using consensus clustering. The Kaplan-Meier method was used to prognosis among the three clusters, and GSVA was used to explore differences in the biological functions. ESTIMATE and single-sample gene-set enrichment analysis (ssGSEA) were used to analyze the tumor immune microenvironment (TME) in different clusters. A risk score signature was developed using a univariate survival analysis and multivariate regression analysis, and the reliability and validity of the signature were verified. By combining the signature with clinical factors, a nomogram was established to predict the prognosis of DLBCL patients. The alluvial diagram and correlation matrix were used to explore the relationship between pyroptosis risk score, clinical features and TME. Results: A large proportion of PRGs are dysregulated in DLBCL and associated with the prognosis. We found three distinct pyroptosis-related clusters (cluster A, B, and C) that differed significantly with regard to the prognosis, biological process, clinical characteristics, chemotherapeutic drug sensitivity, and TME. Furthermore, we developed a risk score signature that effectively differentiates high and low-risk patients. The nomogram combining this signature with several clinical indicators showed an excellent ability to predict the prognosis of DCBCL patients. Conclusions: This work demonstrates that pyroptosis plays an important role in the diversity and complexity of the TME in DLBCL. The risk signature of pyroptosis is a promising predictive tool. A correct and comprehensive assessment of the mode of action of pyroptosis in individuals will help guide more effective treatment.

Acute myelogenous leukemia (AML) is a class of malignant tumors derived from hematopoietic stem or progenitor cells. The H2.0-like homeobox gene (HLX) encodes transcription factors that function in promoting normal hematopoietic cell proliferation and tumor immunity. The present study analyzed the effect of downregulating the HLX on cell cycle distribution and cell proliferation in AML. Moreover, the current study detected changes in the expression of genes and proteins in the Janus kinase (JAK)/STAT signaling pathway to investigate the mechanism of the action of HLX in tumor immunity in AML. HLX expression in AML cell lines was silenced using small interfering siRNA, and MTS/PMS-assay colorimetric assays were used to assess the effect of knockdown of HLX on AML cell proliferation. Flow cytometry was used to analyze changes in cell cycle distribution, while reverse transcription-quantitative PCR and western blotting were used to detect changes in the expression levels of key components of the JAK/STAT signaling pathway, such as p21-activated kinase 1 (PAK1), neuropilin 1 (NRP1), B-cell translocation gene 1 (BTG1) and STAT5. It was found that HLX was differentially expressed in AML cell lines of various subtypes, and HLX expression was higher in the AML/M3 subtype NB4 cell line compared with the control group. Knockdown of HLX in NB4 cells significantly inhibited cell proliferation and arrested cells in the G(0)/G(1) phase. Moreover, STAT5 protein expression, as well as NRP1 and PAK1 expression levels were downregulated, while BTG1 expression was upregulated when HLX was knocked out by siRNA. Collectively, the results suggested that downregulation of HLX may cause G(0)/G(1) phase arrest and inhibit the proliferation of AML cells by activating the JAK/STAT signaling pathway.

Objective: To explore the correlation between the expressions of CD45 as well as CD31 and the prognosis in patients with multiple myeloma. Methods: A prospective cohort study was designed, and 120 patients with multiple myeloma were selected as subjects, among them, 30 patients with CD45 (+) and CD31 (-) were included in CD45 (+) group; 30 with CD31 (+) CD45 (-) were in CD31 (+) group; 30 with CD45 (+) and CD31 (+) were in CD45 (+) CD31 (+) group; 30 with CD31 (-) and CD45 (-) were in CD31 (-) CD45 (-) group. All patients received treatment of bortezomib and long-term follow-up. The objective remission rate (ORR), progression-free survival (PFS) and overall survival (OS) of all patients were observed, and the relationship between the expressions of CD45/CD31 and the prognosis was analyzed in patients after treatment of bortezomib. Results: Analysis of variance showed that there were significant differences in platelets (Plt), lactate dehydrogenase (LDH), beta-2 microglobulin (beta(2)MG), and plasma cell infiltration in bone marrow among the four groups (all P<0.05). SNK-q test showed that the Plt of patients was significantly higher and the beta(2)MG, LDH and plasma cell infiltration in bone marrow were significantly lower in CD45 (+) group, CD31 (+) group and CD45 (+) CD31 (+) group than in CD45 (-) CD31 (-) group (all P<0.05). The distributions of patients with complete response, partial response, stable disease and progressive disease in the four groups were significantly different (P<0.05). The ORR was significant lower in CD45 (-) CD31 (-) group (33.33%) than that in CD45 (+) group (66.33%), CD31 (+) group (60.00%), and CD45 (+) CD31 (+) group (66.67%) (P<0.05), while there was no significant difference between the CD45 (+) group, CD31 (+) group and CD45 (+) CD31 (+) group (P>0.05). The differences in the PFS and OS were significant among the four groups after treatment (both P<0.001). Kaplan-Meier survival analysis suggested that the PFS and OS in the CD45 (-) CD31 (-) group were significantly shorter than those in the CD45 (+) group, CD31 (+) group and CD45 (+) CD31 (+) group after treatment (all P<0.01). Log-rank test showed that there was no significant difference in PFS and OS between CD45 (+) group, CD31 (+) group and CD45 (+) CD31 (+) group (all P>0.05). Cox multiple regression model showed that the factors affecting the prognosis of patients were high LDH, CD45 (-), CD31 (-), and CD45 (-) plus CD31 (-). Conclusion: CD45 (-) and CD31 (-) are related to the poor prognosis in patients with multiple myeloma, and the prognosis between patients with CD45 (+), CD31 (+) or with both CD45 (+) CD31 (+) was not significantly different.

目的 探讨骨髓瘤性胸腔积液(MPE)的流行病学、发病机制、临床表现、治疗及预后.方法 回顾分析2010年10月至2018年7月收治的6例多发性骨髓瘤(MM)合并MPE患者的临床表现、治疗及转归情况,并复习相关文献.结果 6例MPE患者中位发病年龄69(39～82)岁,男女发病无差异,轻链型多见,4例结合形态学和流式细胞术(FCM)诊断.MPE多出现于MM终末期,治疗疗效不佳,中位总生存期仅2.5个月.结论 MPE作为MM的一种少见并发症,胸腔积液FCM有助于提高阳性率,系统化疗联合胸腔局部治疗是主要的治疗手段,但治疗反应率低,预后极差,新药及细胞免疫治疗有望改善预后.

Introduction: This systematic review and meta-analysis aims to explore the influence of ferumoxytol versus placebo on iron deficiency anemia. Methods: We search for randomized controlled trials (RCTs) assessing the effect of ferumoxytol on iron deficiency anemia on PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases. This meta-analysis is performed using the random-effects model. Results: Four RCTs are included in the meta-analysis. Compared with the control group for iron deficiency anemia, intravenous ferumoxytol can significantly improve the proportion of patients with a ≥20 g/L hemoglobin (Hb) increase (RR = 18.43; 95% CI = 7.29–46.57; p < 0.00001), the proportion of patients with an Hb level ≥120 g/L (RR = 18.55; 95% CI = 8.66–39.72; p < 0.00001), transferrin saturation (mean difference = 11.08; 95% CI = 9.86–12.31; p < 0.00001) and FACIT-fatigue score (mean difference = 4.60; 95% CI = 3.21–6.00; p < 0.00001), but has no remarkable influence on adverse events (RR = 1.33; 95% CI = 0.84–2.10; p = 0.22), serious adverse events (RR = 1.22; 95% CI = 0.74–2.02; p = 0.44), and death (RR = 0.32; 95% CI = 0.05–1.95; p = 0.22). Conclusions: Intravenous ferumoxytol can provide the important benefits for iron deficiency anemia.

Objective: To investigate the hyaluronic acid (HA) modified, doxorubicin (DOX) and gallic acid (GA) co-delivered lipid-polymeric hybrid nano-system for leukemia therapy. Methods: We produced a kind of lipid-polymer hybrid nanoparticle (LPHN) with a core-shell structure in which DOX and GA were co-loaded. In vitro and in vivo leukemia therapeutic effects of the HA modified, DOX and GA co-delivered LPHNs (HA-DOX/GA-LPHNs) were evaluated in DOX resistant human HL-60 promyelocytic leukemia cells (HL-60/ADR cells), DOX resistant human K562 chronic myeloid leukemia cells (K562/ADR cells), and HL-60/ADR cells bearing mouse model. Results: The sizes and zeta potentials of HA modified LPHNs were about 160 nm and -40 mV. HA-DOX/GA-LPHNs showed the most prominent cytotoxicity and the best synergistic effect was obtained when DOX/GA ratio was 2/1. In vivo studies revealed that HA-DOX/GA-LPHNs inhibited tumor growth from 956 mm3 to 213 mm3, with an inhibition rate of 77.7%. Conclusion: In summary, the study showed that HA-DOX/GA-LPHNs can be applied as a promising leukemia therapy system.

急性早幼粒细胞白血病(APL)是一种具有特异染色体核型和基因改变的白血病,90％的患者存在典型的t(15;17),而99％的患者可检测到PML-RARα融合基因[1].APL可同时伴随其他染色体的异常,而伴随获得性21三体的报道较为罕见[2].笔者报道1例以获得性21三体为唯一细胞遗传学异常的APL并复习相关文献.

BACKGROUND T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy caused by abnormal proliferation of immature T cell progenitors. Chemotherapy of T-ALL usually consists of induction, consolidation, and long-term maintenance. Diacetyl hexamethylene diamine (CAHB) is a newly developed agent that induces the differentiation of malignant cells and deprives their clonal growth ability. Since its effect on T-ALL has not been previously determined, we evaluated its potential function in the Jurkat cell line. MATERIAL AND METHODS MTT assay was conducted to evaluate the cytotoxicity and anti-proliferative effect of CAHB. The apoptosis level of CAHB-treated Jurkat cells was evaluated using flow cytometry via staining with Annexin V/PI or cleaved-caspase-3. The alteration of mitochondrial membrane potential was determined by flow cytometry. The expression of Bax and Bcl-2 was evaluated by RT-PCR and Western blot. Western blot was also used to assess the activation of Akt. RESULTS CAHB inhibited the proliferation and promoted the apoptosis of Jurkat cells in a time- and dose-dependent manner by decreasing activation of Akt, reducing the mitochondrial membrane potential, and downregulating the Bcl-2/Bax ratio. CONCLUSIONS Our data suggest that CAHB might be regarded as a novel treatment agent for T-ALL since it can induce apoptosis and inhibit proliferation of the T-ALL cell line at a relatively low level.

Objective To investigte the correlation between HLX expression level and AML's clinical variables and different risk stratification.Methods A rcal-time quantitative PCR was used to detect HLX expression in the bone marrow mononuclear cells of 32 de novo AML patients with initial treatment.The relationship between HLX expression level and clinical parameters (FAB classification,hemogram,bone marrow progenitor cells,differentiation and different risk stratification) was investigted.Results The HLX expression of patients with AML was significantly decreased in AML-M3 (P ＜ 0.01),and increased in AML-M5 (P ＜ 0.05).It was negatively correlated with bone marrow progenitor cells (P ＜ 0.01),and was positively correlated with the number of peripheral blood platelet (P ＜0.05).The expression of HLX in AML-M3 was positively correlated with peripheral blood leukocyte levels (P ＜ 0.05),and it was negatively correlated with leukocyte cell level in peripheral blood in AML-M5 (P ＜ 0.05).In AML-Ms groups,the expression levels of HLX of poorly differentiated group were significantly higher than those of the well-differentiated groups (P ＜ 0.05).In AML patients with initial treatment in patient group and non-M3 group,there was no significant difference between the low-risk group and the central risk group (P ＞0.05).Conclution HLX expression levels were elevated in some subtypes,such as AML-M5.and there were differences in different FAB types.HLX gene is associated with the proliferation,differentiation and maturation of leukemia cells.However there was no evidence that HLX is different in different AML risk stratification,which needs further experimental studies.

Objective To investigate the expression of HLX gene in leukemia cell lines,and to analyze the growth of cells and the expression of PAK1 gene by inhibiting HLX expression with RNA interference technique.Methods According to HLX gene coding sequence,siRNA-HLX was transfected into AML / M3 subtype NB4 cells to inhibition the HLX gene,and the expression of HLX gene and PAK1 gene was detected by qRT-PCR,and the cell growth was observed by fluoresccncc phase contrast microscope,MTS / PMS was used to detect proliferation inhibition rate.Results The expression of HLX gene in AML cell lines was significantly higher than that in control group (P ＜ 0.01).When HLX gene was down-regulated,the expression of PAK1 mRNA was also down-regulated (P ＜0.01),and AML cells grow slowly and its proliferation is inhibited.Conclusion HLX gene can inhibit the growth,proliferation and differentiation of AML cell lines.