Double expressor lymphoma (DEL), characterized by high expressions of both MYC and BCL-2, displays poor prognosis after current therapies. The HDAC inhibitor chidamide has been approved for treatment of T cell lymphoma, but its efficacy on B cell lymphoma is unclear. Here, by combining inhibition screening and transcriptomic analyses, we found that the sensitivity of B lymphoma cells to chidamide was positively correlated with the expression levels of MYC. Chidamide treatment reduced MYC protein levels and repressed MYC pathway in B lymphoma cells with high MYC expressions. Ectopic expression of MYC in chidamide-insensitive B lymphoma cells increased their response to chidamide. Thus, we proposed that adding chidamide into R-CHOP (CR-CHOP) might be effective for DEL, and retrospectively analyzed 185 DEL patients treated in West China Hospital. 80% of patients showed response to CR-CHOP treatment. In the median follow-up of 42 months, CR-CHOP significantly improve the survival for DEL patients with R-IPI ≤2. Totally 35 patients underwent autologous stem cell transplantation (ASCT) in remission and demonstrated a trend for better survival. Combining CR-CHOP with ASCT resulted in the most superior PFS and OS above all. For response patients, CR-CHOP reduced relapse with better PFS than R-CHOP-like regimens with or without ASCT. Taken together, our data indicated that chidamide repressed the MYC pathway in B lymphoma and is potentially efficacious to treat DEL.

Abstract Objective For traumatic lower extremity artery injury, it is unclear whether it is better to perform endovascular therapy (ET) or open surgical repair (OSR). This study aimed to compare the clinical outcomes of ET versus OSR for traumatic lower extremity artery injury. Methods The Medline, Embase, and Cochrane Databases were searched for studies. Cohort studies and case series reporting outcomes of ET or OSR were eligible for inclusion. Robins-I tool and an 18-item tool were used to assess the risk of bias. The primary outcome was amputation. The secondary outcomes included fasciotomy or compartment syndrome, mortality, length of stay and lower extremity nerve injury. We used the random effects model to calculate pooled estimates. Results A total of 32 studies with low or moderate risk of bias were included in the meta-analysis. The results showed that patients who underwent ET had a significantly decreased risk of major amputation (OR = 0.42, 95% CI 0.21–0.85; I2=34%) and fasciotomy or compartment syndrome (OR = 0.31, 95% CI 0.20–0.50, I2 = 14%) than patients who underwent OSR. No significant difference was observed between the two groups regarding all-cause mortality (OR = 1.11, 95% CI 0.75–1.64, I2 = 31%). Patients with ET repair had a shorter length of stay than patients with OSR repair (MD=-5.06, 95% CI -6.76 to -3.36, I2 = 65%). Intraoperative nerve injury was just reported in OSR patients with a pooled incidence of 15% (95% CI 6%–27%). Conclusion Endovascular therapy may represent a better choice for patients with traumatic lower extremity arterial injury, because it can provide lower risks of amputation, fasciotomy or compartment syndrome, and nerve injury, as well as shorter length of stay.

The authors have disclosed no conflicts of interest.

OBJECTIVE:Despite the availability of new agents, elderly patients with multiple myeloma (MM) usually present with poor outcomes due to the heterogeneity of disease conditions, especially immune deficiency. Regulatory B cells (Bregs) can be involved in immune defects by exerting immune regulatory functions in MM. In order to provide more evidence-based practice for the elderly MM, the study established and assessed a stratified therapeutic model with studies on Bregs for Chinese Elderly Multiple Myeloma in 2021 (CEMM2021). METHODS:In this open-label, non-interventional, prospective study in the real world, 159 newly diagnosed MM (NDMM) patients over 65 years old were sequentially recruited and bone marrow aspirates prior to treatment were obtained to detect the ratios of Bregs by flow cytometry. RESULTS:Based on the CEMM2021 model, 147 patients had received at least one cycle of induction therapy, including bortezomib/dexamethasone (Bd) (n = 80), lenalidomide/dexamethasone (Rd) (n = 27), Bd with a third agent X (Bd + X) (n = 27), and other regimens (n = 13). The proportions of patients achieving very good partial response or better were comparable among Bd, Bd + X, and Rd groups (41.9% vs. 54.5% vs. 44.0%, p = 0.472). Besides, the progression-free survival (PFS) and overall survival (OS) were not significantly different among Rd, Bd, and Bd + X groups. Multivariable analysis showed that induction efficacy less than partial response (PR) were poor prognostic factors for PFS, while Revised-International Staging System (R-ISS) III and efficacy less than PR were poor prognostic factors for OS. This study also found that the ratios of bone marrow Bregs <10% (p = 0.036) and SUVmax of PET-CT scan >4.2 (p = 0.000) were closely correlated with OS in the elderly MM. CONCLUSIONS:For the elderly NDMM, the CEMM2021 algorithm in our center might provide a valuable reference for the guidance of therapeutic strategies, with the combination of Bregs resulting in an effective and clinically meaningful prediction in contemporary treatment.

Objective: Isolated mesenteric artery dissection (IMAD) is an increasingly diagnosed disease. However, multicentre studies to support clinical decision making are limited. This multicentre retrospective study aimed to investigate the characteristics, treatment options, and outcomes of IMAD. Methods: Data from consecutively enrolled patients with IMAD between October 2009 and May 2021 at three hospitals were collected retrospectively. One hundred and ninety uncomplicated symptomatic IMAD patients were divided into two groups: conservative (n = 141) and operative (n = 49). The costs, length of hospital stay, factors affecting outcomes, symptom relief, and complete remodelling of superior mesenteric artery (SMA) were analysed between the two groups. Results: Compared with patients who received operative treatment, patients receiving conservative treatment had shorter hospital stays (8.2 +/- 4.6 vs. 11.9 +/- 6.4 day, p <.020) and lower hospital costs (14 900 +/- 1 048 vs. 60 400 +/- 7 733 yuan, p <.001). In contrast, patients receiving operative treatment showed higher complete SMA remodelling (95.9% vs. 51.8%, p <.001). The cumulative rate of symptom relief was similar between the groups (p = .71). The rates were 78% vs. 79%, 87% vs. 87%, 89% vs. 87% at one, 12, and 60 months in the conservative and operative groups, respectively. Further subgroup analysis showed that endovascular treatment of IMAD had the advantage of shorter hospital stays than open surgery (10.7 +/- 4.5 vs. 25.2 +/- 9.4 days, p <.010). Univariable analysis showed that Sakamoto type II was associated with failed complete SMA remodelling (odds ratio 0.34; 95% confidence intervals 0.13 - 0.91; p = .031). Conclusion: IMAD patients achieved good long term survival and symptom relief regardless of the treatment. Sakamoto type II IMAD is a risk factor for failed complete SMA remodelling. Although endovascular treatment provided a higher rate of complete SMA remodelling, the conservative group had statistically significantly shorter hospital stays, lower hospital costs, and similar cumulative rates of symptom relief. Therefore, this study supports conservative treatment as the main strategy for uncomplicated symptomatic IMAD patients.

Objective Acute mesenteric ischemia is a disease with high morbidity and mortality, and it is traditionally treated with open surgery. Endovascular therapy and hybrid techniques are alternative treatments that are also currently available. We performed a meta-analysis to evaluate the outcomes of the different treatment approaches in the last 20 years. Methods Studies on acute mesenteric ischemia that were indexed in PubMed, Embase, and MEDLINE databases (from January 1, 2000, to April 1, 2021) were reviewed. All related retrospective observational studies and case series were included. A random-effects model was used to calculate pooled estimates, and the results were reported as proportions and 95% confidence intervals (CIs). Results In our study, a total of 2369 patients (in 39 studies) underwent endovascular, open surgery, or retrograde open mesenteric stenting. The pooled mortality estimates for open surgery, endovascular therapy, and retrograde open mesenteric stenting were 40% (95% CI, 0.33–0.47; I2 = 84%), 26% (95% CI, 0.19–0.33; I2 = 33%), and 32% (95% CI, 0.21–0.44; I2 = 26%), respectively. Conclusions The mortality associated with open surgical treatment, endovascular therapy, and retrograde open mesenteric stenting tend to be similar in the last 20 years.

Macrophage migration inhibitory factor (MIF) has been shown to promote disease progression in many malignancies, including multiple myeloma (MM). We previously reported that MIF regulates MM bone marrow homing and knockdown of MIF favors the extramedullary myeloma formation in mice. Here, based on MIF immunostaining of myeloma cells in paired intramedullary and extramedullary biopsies from 17 patients, we found lower MIF intensity in extramedullary MM (EMM) versus intramedullary MM (IMM). Flow cytometry and histology analysis in xenograft models showed a portion of inoculated human MM cells lost their MIF expression (MIFLow) in vivo. Of note, IMM had dominantly MIFHigh cells, while EMM showed a significantly increased ratio of MIFLow cells. Furthermore, we harvested the extramedullary human MM cells from a mouse and generated single-cell transcriptomic data. The developmental trajectories of MM cells from the MIFHigh to MIFLow state were indicated. The MIFHigh cells featured higher proliferation. The MIFLow ones were more quiescent and harbored abundant ribosomal protein genes. Our findings identified in vivo differential regulation of MIF expression in MM and suggested a potential pathogenic role of MIF in the extramedullary spread of disease.

BACKGROUNDAnti‐E is the most common and important RBC alloantibody in the Chinese population. Several studies have demonstrated that the production of specific RBC alloantibodies is associated with HLA‐DRB1 polymorphisms. Considering that the Chinese population has its own unique characteristics of HLA‐DRB1 polymorphisms, we investigate whether specific HLA‐DRB1 alleles are associated with E immunization in a Chinese population.STUDY DESIGN AND METHODSThe frequencies of HLA‐DRB1 phenotypes were compared among 78 patients possessing anti‐E and 192 healthy blood donors. HLA‐DRB1 genotyping was carried out using sequence‐based typing method. The TEPITOPEpan software was used to predict E antigen–derived anchor peptides binding to HLA‐DRB1 molecules.RESULTSThe frequency of HLA‐DRB1*09:01 phenotype was significantly higher in the patients with anti‐E than in healthy controls: 76.9% versus 27.6% (odds ratio, 8.7; 95% confidence interval, 4.7‐16.2; corrected p value < 0.0034). One E antigen–derived anchor peptide (217WMFWPSVNS225) was predicted to bind three HLA‐DRB1 molecules (HLA‐DRB1*04:05, *04:17, and *13:02); however, no anchor peptide was predicted to bind HLA‐DRB1*09:01.CONCLUSIONThis study indicated that HLA‐DRB1*09:01 phenotype was significantly more prevalent in E‐immunized patients than the control group. It suggested that HLA‐DRB1*09:01 molecule might represent a susceptibility phenotype enhancing formation of anti‐E alloantibody. Further study would be necessary to identify the anchor peptide responsible for E alloimmunization by stimulation of specific T cells by peptide originating from E antigen.

Abstract Background: DNA hypomethylating agent, decitabine, has become the current standard therapy for patients with higher-risk myelodysplastic syndromes (MDS). Decitabine was launched in China in August 2009 without clinical trials. According to some retrospective studies, the efficacy and safety are similar to those reported in other countries, but there is still a lack of large-scale prospective clinical trials. So we start a prospective clinical trial in China to compare the effect and safety of decitabine in MDS, which was registered at clinicaltrials.gov (NCT02013102). Design: Adults with intermediate or high risk MDS by the International Prognostic Scoring System (IPSS≥0.5) were randomized to receive either decitabine 20 mg/m2 IV daily for 5 days (arm Ⅰ) or decitabine 12 mg/m2 IV daily for 8 days (arm Ⅱ) every four weeks. Patients continued to receive study drug for 4 cycles until death, disease progression, intercurrent illness preventing further administration of treatment, unacceptable adverse event or decision by the patient to withdraw from the study. And supportive care were permitted. The primary end point was overall response rate (ORR, CR+mCR+PR) by International Working Group (IWG 2006) criteria, secondary end points included CR, mCR, PR, HI, safety, et al. Results: We enrolled a total of 198 patients between 8/2013 and 12/2017, among which 7 patients didn't take decitabine, and 191 were included in the analysis. 94 in arm Ⅰ recieved decitabine and 97 in arm Ⅱ. 32.8% of patients withdrew from the study for a variety of reasons, including progression and death (5.1%), personal decision (13.6%), adverse events (6.6%), and other causes (7.6%). The median age of patients in arm Ⅰ was 54.88 years old and 54.82 years old in arm II. The median follow-up was 106 days for patients in both arms. The patients received a mean 2.5 cycles of decitabine therapy for arm Ⅰ and 2.0 cycles for arm Ⅱ. The overall response rate was 39.3% in total, and 41.5% and 38.1% (p=0.6598) for patients in arm Ⅰ and arm Ⅱ, respectively. And CR was 18.1% and 14.4% (p= 0.5584) , PR was 6.4% and 3.1% (p=0.3257) , mCR was 17.0% and 20.6% (p=0.5814) , HI was 3.2% and 1.0% (p=0.3633) , for patients in armⅠand armⅡ, respectively (Table 1). Among all patients, 38.7% were intermediate-1 risk, 40.3% were intermediate-2 risk, 20.4% were high risk. Analysis of response by MDS patient subtypes is shown in Table 2. Those who were higher risk experienced higher ORR and CR, while the difference is not significant between two arms (p>0.05). As expected, cytopenias were the most frequent complications (76.4%). Grade 3-4 neutropenia, thrombocytopenia and anemia considered to be at least possibly related to the study drug occurred at rates of 23.0%, 34.6%, and 34.6% of patients, respectively. Nonhematologic adverse events were also common including abnormal metabolism and nutrition (23.40% vs 18.56%), abnormal gastrointestinal function (29.79% vs 41.24%), cardiac disorders (11.70% vs 14.43%), infection and infectious diseases (32.98% vs 36.08%), abnormal skin and subcutaneous tissue and so on, which were no significant differences between two ams. During the study there were 17 SAE, only 7 cases were possibly related to drug therapy, such as pulmonary infection, Sepsis, myelosuppression, intracranial hemorrhage, hepatic failure, and arrhythmia. Conclusions: The use of 5-day and 8-day schedule decitabine is safe and effective in patients with intermediate and high risk MDS, among which there was no significant differences. Disclosures No relevant conflicts of interest to declare.

Background Rhnull is a rare autosomal recessive phenotype, which is characterized by the lack of Rh antigen expression on the red blood cells (RBCs). Rhnull of the regulator type is caused by RHAG mutation. In this study, a novel nonsense mutation in RHAG gene was identified in a Chinese Rhnull individual. Objectives and methods Rh phenotypes of the Rhnull individual and his family members were typed by standard serological methods. DNA sequences of all ten exons of RHAG gene were analyzed using genomic DNA by polymerase chain reaction (PCR) and direct-sequencing. Results Serological testing results showed a D-C-c-E-e- phenotype in the proband. Molecular analyses revealed a 540C > A mutation in exon 4 of RHAG gene was present at the homozygous state in the proband. His parents were heterozygous for the mutation, and his brother didn't carry the mutation. The 540C > A mutation was nonsense mutation, which led to a premature stop codon (Tyr180stop). Conclusion These results indicated that the 540C > A nonsense mutation in RHAG gene caused the regulator type of Rhnull phenotype in a Chinese individual. Our results contributed to a greater understanding of the genetic mechanisms of Rhnull phenotype.

TransfusionVolume 56, Issue 3 p. 771-772 REPORT OF NEW ALLELES OR ANTIGENS A novel A allele with multiple missense mutations in Exon 7 identified in a Chinese individual Li Hou, Li Hou Department of Hematology, Hematology Research Laboratory, West China Hospital, Sichuan University, Chengdu, SichuanSearch for more papers by this authorLi Tian, Corresponding Author Li Tian Department of Blood Immunology, Institute of Blood Transfusion, Chinese Academy of Medical Sciences, Chengdu, Sichuan, ChinaAddress reprint requests to: Li Tian, Department of Blood Immunology, Institute of Blood Transfusion, Chinese Academy of Medical Sciences, Chengdu, Sichuan 610052, China; e-mail: watercrowd@tom.com.Search for more papers by this author Li Hou, Li Hou Department of Hematology, Hematology Research Laboratory, West China Hospital, Sichuan University, Chengdu, SichuanSearch for more papers by this authorLi Tian, Corresponding Author Li Tian Department of Blood Immunology, Institute of Blood Transfusion, Chinese Academy of Medical Sciences, Chengdu, Sichuan, ChinaAddress reprint requests to: Li Tian, Department of Blood Immunology, Institute of Blood Transfusion, Chinese Academy of Medical Sciences, Chengdu, Sichuan 610052, China; e-mail: watercrowd@tom.com.Search for more papers by this author First published: 12 January 2016 https://doi.org/10.1111/trf.13466Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume56, Issue3March 2016Pages 771-772 RelatedInformation

BACKGROUND: Rh-null is a rare autosomal recessive disorder, and Rh-null of the regulator type may result from mutation of the RHAG gene, which encodes RhAG glycoprotein and modulates Rh antigen expression. This study described the molecular genetic analysis of a Chinese Rh-null family and identified a novel mutation in the RHAG gene.STUDY DESIGN AND METHODS: RBCs from the Rh-null family members were analyzed for Rh phenotype by standard methods. DNA sequences of all 10 exons of RHAG gene were analyzed using genomic DNA by polymerase chain reaction and direct DNA sequencing.RESULTS: Genomic DNA analyses showed that a 672C>A mutation in Exon 5 of the RHAG gene was present at the homozygous state in DH and at the heterozygous state in the other members of the Rh-null family. The 672C>A missense mutation converted serine into arginine at Position 224 in the Transmembrane Segment 7 of RhAG glycoprotein.CONCLUSION: These findings provide evidence that the 672C>A missense mutation in the RHAG gene could result in Rh-null of the regulator type, and the single-amino-acid change (Ser to Arg) might be critical for assembly of the Rh antigen complex within the membrane.

Wiskott–Aldrich syndrome (WAS) is an X-linked recessive disorder characterized by thrombocytopenia, small platelets, eczema, increased susceptibility to infection, and immunodeficiency. Mutations of the Wiskott–Aldrich syndrome protein (WASP) gene are responsible for this severe congenital disease. In this study, we report on a 2-year-old Chinese boy who presented with classic clinical WAS manifestations. By direct sequencing of cDNA and genomic DNA of the patient, we identified a novel mutation: the first nucleotide in exon 8 (G) had been deleted (769delG). This mutation results in two kinds of aberrant mRNA with abnormal splicing and causes frameshift and a stop codon at amino acid 260. Western blotting demonstrated a 28-kDa truncated WAS protein. A maternal study revealed that his mother had a heterozygous genotype, but showed normal WASP expression.

As main hematopoietic organ, bone marrow have three dimensional microenvironment for hematopoietic stem/progenitor cells grow in, so call “hematopoietic cells niche”, which are composed by stromal cells and extracelluar matrix. The interactions of cell to cell and cell to matrix between stem/progenitor cells with hematopoietic niche are facilitated by its three dimensional conformation. The biology behaviors of hematopoietic stem cells are mediate by many signal transductions between stem/progenitor cells with their corresponding microenvironment. Now there are strong evidence from animal model study suggests that osteoblasts might play an essential role in creation of a hematopoietic stem cell niche and thereby regulation of stem cell maintenance, proliferation, and maturation. In light of the structure-function relationship of bone marrow topography, we conceived a biomimetic culture system (3D culture system) with bio-derived bone as framework, composited with human marrow mesenchymal stem cells, and induced the cells into osteoblasts to simulate the effects of hematopoietic osteobalst niche. CD 34+ cells or mononuclear cells separated from umbilical cord blood were cultured for 2∼5 weeks in the 3D culture system and also in a conventional 2D culture system as control without additional cytokine supplement. Based on our results, higher expression of extracelluar matrix and N-cadherin were observed in 3D culture system compared to 2D system. At 2 weeks culture, 3D culture system showed higher number of CD34+ cells and CD34+/CD38- cells when compared with the input (P<0.05), the increased cells were predominant CD34+/CD38-cells. Although CD34+ cells were decreased at 5 weeks culture; nevertheless, CD34+/CD38- cells were still maintained at high level. We also observed that imbedding MNCs with a higher percentage of CD34+/CD38-cells cultured in 3D system (P<0.05), which may represent a down regulation of CD38 phenotype during culture. The function of cultured cells was evaluated in colony forming unit (CFU) assay and long term culture initial cell (LTC-IC) assay. 3D system produced higher expansion of CFU progenitors than 2D system (7.13–8.89 times vs. 1.22–1.31times) after 2 weeks culture. Of note, the colony distribution of 3D system manifested higher percentage of BFU-E and CFU-GEMM, while 2D system showed mainly CFU-GM. LTC-IC represents the primitive progenitor, 3D system showed a 6.2 times increment over input after 2 weeks culture. Furthermore, it was competent to maintain the immaturation of hematopoietic progenitor cells (HPCs) over 5 weeks. This study demonstrated that our 3D culture system constructed with the bio-derived bone composited with induced osteoblast is capable to allow maintenance and expansion of primitive hematopoietic progenitor cells in vitro. It may open a new avenue to study HSCs/HPCs behaviors and to achieve sustained primitive progenitor cell expansion.

The relationship between mitochondria gene mutation and hematological malignancies has been focusing on as a key point in recent studies. This study was aimed to investigate whether in patients with myelodysplastic syndrome (MDS) exists mitochoudria cytochrome oxidase COI and COII gene mutations different from normal tissues and to analyze whether these mutations are "hot spot" mutations. Eighteen MDS patients aged from 20 to 70 years old were brought into this study, including 2 of RA, 3 of RCMD, 7 of RAEB, 5 of AML (transformation from MDS), and 1 of MDS/MPD. The total DNA was extracted both from bone marrow cells and buccal cells of the same patients. A pair of primers was designed to amplify a fragment with 528 base pair (7181 - 7709) by PCR technique, which contained high frequency mutation area of cytochrome oxidase COI and COII gene based on the literature reports. The PCR products were purified and sequenced as bidirection to confirm if there is any mutation. The results of sequence of COI and COII gene from MDS patient bone marrow cells were compared with both the standard sequence from GenBank and the sequence from MDS patient buccal cells. The results showed that 3 single nucleotide changes in 528 bp cytochrome oxidase gene fragment from 18 MDS patients were confirmed. They were 7674 T-->C, 7353 A-->G, and an insert mutation of G at 7702. The former two mutations caused isoleucine-->methionine, and methionine-->viline. The 7702G ins was only confirmed with marrow cells in a patient, and caused a frame shift, which suggested that the mutation might be related to MDS cells. It is concluded that some of "hot spots" of mtDNA mutation in cytochrome oxidase (COI, COII) gene from our MDS patients are failed to be confirmed, but 3 new mutations on this gene are found, which suggested that mitochondria DNA mutations in MDS patients still have much complexity and heterogeneity, mtDNA mutation may be a prophase or an accompany phenomenon of this disease.

We constructed a “biomimetic osteoblast niche” with bio-derived bone as a scaffold, on which we seeded marrow mesenchymal stem cells (MSCs) from CML patients, and induced the MSCs to differentiate into osteoblasts. Bone marrow mononuclear cells from CML patients were cultured in the biomimetic niche (3D culture system) or a 2D culture system with the induced MSCs/osteoblasts as a feeder cell layer for 2 and 5 weeks without adding exogenous cytokines. Cultured cells were analyzed regarding their phenotypes and functions using flow cytometry, colony-forming unit (CFU) assay and long-term culture-initiating cells (LTC-IC) assay. All cultured and colony cells in the LTC-IC assay were collected and analyzed by fluorescent in situ hybridization to identify Ph (bcr/abl)-positive cells. Our results showed that all parameters were higher in the 3D than in the 2D system, either at 2 or 5 weeks, i.e., regarding the number of CD34+ cells (8,277.00 vs. 4,490.75 or 2,276.75 vs. 786.00 per well on average, respectively), number of CD34+/CD38− cells (1,207.50 vs. 474.25 or 497.25 vs. 114.25 per well on average, respectively), numbers of CFUs (103.33 vs. 79 or 47.0 vs. 21.67/105 MNCs; 189.33 vs. 131.00 or 10.33 vs. 3.67 per well on average, respectively), frequency of LTC-ICs (2.23 × 10−5 vs. 1.40 × 10−5 or 1.86 × 10−5 vs. 0.64 × 10−5, respectively) and number of remaining LTC-ICs (2.80 vs. 2.03 or 0.46 vs. 0.07 per well on average, respectively). The Ph (bcr/abl)-positive cell fraction was reduced in both systems during culture, but in the 3D system, it was not as rapid as in the 2D system and showed a leukemic predominance. In conclusion, our “biomimetic osteoblast niche” might provide a more adaptive microenvironment for leukemic stem/progenitor cell growth. The biological characteristics of leukemic stem/progenitor cells were partially maintained. It was suggested that the 3D biomimetic niche might be a new tool for studying the behaviors of leukemic hematopoietic stem cells/hematopoietic progenitor cells in vitro.

Myelodysplastic syndromes are refered to as a group of diseases characterized by abnormal clonal proliferation of hematopoietic stem cells with pancytopenia and dysplasia. Recently, it has been documented that ringed sideroblasts are not only confined to the refractory anemia with ring sideroblast (RARS) subtype of MDS, but also contribute to numerous underlying MDS pathophysiological processes as a significant feature of dysplasia. This clonal heterogeneity suggested a pathogenetic role of mitochondrial DNA mutation. Many studies have shown that mitochondrial respiratory chain defects resulting from mutation of mitochondrial DNA may lead to multiple pathophysiologic changes, and may impact on the pathogeneses of MDS.