间充质干细胞对再生障碍性贫血患者造血支持及T淋巴细胞分泌功能的影响

BACKGROUND: Recently, the role of mesenchymal stem cells in aplastic anemia has been widely explored. However, its underlying mechanism remains unclearly.OBJECTIVE:To study the effect of umbilical cord blood and bone marrow mesenchymal stem cells on hematopoietic support and secretory function of T lymphocytes in patients with aplastic anemia.METHODS:Cord blood and bone marrow samples from 48 cases of aplastic anemia and 48 healthy lying-in women to isolate mesenchymal stem cells using flow cytometry. Mesenchymal stem cells from the cord blood and bone marrow were respectively co-cultured with cord blood mononuclear cells to count burst forming units-erythroid and colony forming units-granulocyte/macrophage. Mesenchymal stem cells were co-cultured with T lymphocytes from aplastic anemia patients undergoing phytohemagglutinin stimulation, and ELISA was used to detect interleukin-2, interleukin-4 and interferon-γ levels secreted from T lymphocytes.RESULTS AND CONCLUSION: The number of burst forming units-erythroid and colony forming units-granulocyte/macrophage significantly increased in normal bone marrow or umbilical cord blood mesenchymal stem cells co-cultured with cord blood mononuclear cells (P < 0.05), but reduced remarkably in umbilical cord blood mesenchymal stem cells from aplastic anemia patients co-cultured with cord blood mononuclear cells (P < 0.05). Levels of interleukin-2, interleukin-4 and interferon-γ from T lymphocytes were inhibited significantly after co-culture with normal bone marrow mesenchymal stem cells compared with phytohemagglutinin-induced T lymphocytes (P < 0.05). There was a similar inhibitory effect after co-culture with normal umbilical cord blood mesenchymal stem cells. There was a significantly reduction in the capacity of inhibiting interleukin-2, interleukin-4 and interferon-γ levels from T lymphocytes after co-culture with bone marrow mesenchymal stem cells from aplastic anemia patients (P < 0.05). Aplastic anemia patients show some functional defects in their bone marrow mesenchymal stem cells that have a weaker inhibitory role than normal bone marrow or umbilical cord blood mesenchymal stem cells in the hematopoietic support and secretory function of T lymphocytes. These findings indicate that mesenchymal stem cells from aplastic anemia patients can influence the pathological progress through weakening hematopoietic support and secretory function of T lymphocytes.  中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

Natural Killer Cells： Biology and Clinical Use in Cancer Therapy

Natural killer (NK) cells have the ability to mediate both bone marrow rejection and promote engraftment,aswell as the ability to elicit potent anti-tumor effects.However the clinical results for these processes are stillelusive.Greater understanding of NK cell biology,from activating and inhibitory receptor functions to the roleof NK cells in allogeneic transplantation,needs to be appreciated in order to draw out the clinical potential ofNK cells.Mechanisms of bone marrow cell (BMC) rejection are known to be dependant on inhibitory receptorsspecific for major histocompatibility complex (MHC) molecules and on activating receptors that have manypotential ligands.The modulation of activating and inhibitory receptors may hold the key to clinical successinvolving NK cells.Pre-clinical studies in mice have shown that different combinations of activating andinhibitory receptors on NK cells can reduce graft-versus-host disease (GVHD),promote engraftment,andprovide superior graft-versus-tumor (GVT) responses.Recent clinical data have shown that the use ofKIR-ligand incompatibility produces tremendous graft-versus-leukemia effect in patients with acute myeloidleukemia at high risk of relapse.This review will attempt to be a synthesis of current knowledge concerning NKcells,their involvement in BMT,and their use as an immunotherapy for cancer and other hematologicmalignancies.Cellular & Molecular Immunology.2004;1(1):12-21.     

Research hotspot of biological scaffold materials promoting osteogenic differentiation of bone marrow mesenchymal stem cells北大核心

BACKGROUND: At present, a single biological scaffold material is difficult to meet the osteogenic needs of bone tissue engineering, and bone marrow mesenchymal stem cells have excellent osteogenic characteristics. Composite scaffolds and scaffolds combined with growth factors have better osteogenic ability. It is a research hotspot at present. OBJECTIVE: To review different biological scaffolds and their modified scaffolds to promote the osteogenic differentiation of bone marrow mesenchymal stem cells. METHODS: The related articles published in CNKI, Wanfang, VIP, PubMed and Embase databases from January 2014 to July 2020 were searched by the first author with the keywords of “bone marrow mesenchymal stem cells, scaffolds, osteogenic differentiation, hydroxyapatite, collagen, chitosan” in English and Chinese. Finally, 69 articles were selected. RESULTS AND CONCLUSION: The rapid development of bone tissue engineering can effectively solve the problem of bone defect repair. Seed cells and biological scaffold materials are the core of bone tissue engineering. Bone marrow mesenchymal stem cells have excellent osteogenic differentiation ability and are widely used in bone tissue engineering. The combination of different scaffold materials, the use of advanced preparation technology, or the surface modification of scaffolds and the addition of growth factors can fully combine the advantages of various biological scaffold materials, induce the osteogenic differentiation of bone marrow mesenchymal stem cells and the formation of scaffold blood vessels, and achieve the purpose of repairing bone defects, and is the research focus of bone tissue engineering. © 2022, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

Classification of myeloproliferative disorders in cats using criteria proposed by the animal leukaemia study group: A retrospective study of 181 cases (1969–1992)

Bone marrow cytology in Wright or Wright Giemsa stained smears from 181 feline patients were evaluated according to recently published criteria by the animal leukaemia study group for classification of acute] myeloid leukaemas (AML) and myelodysplastic syndrome (MDS). AML was recognised in 107 (59.1%) and MDS in 39 (21.5%) cats. The frequency of acute myeloblastic leukaemia (M1 and M2 combined) was high (30.9%), erythroleukaemia (M6 and M6-Er combined) was relatively less frequent (17.1%), and acute undifferentiated leukaemia (AUL), acute monoblastic leukaemia (M5) and acute myelomonocytic leukaemia (M4) were less common, each with an incidence of less than 5.0%. Most of the M1 cats had greater than 70.0% blast cells in bone marrow compared to only a few of the M2 cats. Some blast cells in occasional AUL cats showed cytoplasmic differentiation to either erythroid or myeloid lineage or rarely to both. Type I (classical) myeloblasts predominated in all Ml cats, but occasional type II myeloblasts were seen in some cats and a few cats had some type III myeloblasts. Rubriblasts were prominent in most of the M6-Er cats. Dysplastic changes were more common in M2 than in M1 cats and included primarily dysgranulopoiesis (giant metamyelocytes and bands) and dyserythropoiesis (megaloblastic rubriblasts and rubricytes) and rarely dysmegakaryocytopoiesis (abnormal nuclear morphology). Dysplastic changes involving primarily the erythroid series were seen in M6 and M6-Er cats. Dysmyelopoiesis, in the form of occasional giant metamyelocytes and band neutrophils, was also seen in most cats considered to have myeloid hyperplasia unassociated with leukaemia or MDS. Two M2 and two MDS cats had high (>10.0%) eosinophils in bone marrow and were designated M2-Eos and MDS-Eos, respectively. Cytochemical staining was performed on bone marrow smears from 65 cases to demonstrate myeloid markers such as alkaline phosphatase (ALP), peroxidase (PO), chloroacetate esterase (CAE), and Sudan black B (SBB) and monocytic markers such as α-naphthyl acetate esterase (NAE) and a-naphthyl butyrate esterase (NBE). NAE and NBE staining reactions were usually complementary. Cytochemical heterogeneity and lineage infidelity were observed in some AML subtypes. Blast cells were positive for myeloid markers in many but not all cases of Ml and M2. Similarly monocytic markers were evident in some but not all cases of M4 and M5. Monocytic markers were also evident in blast cells of one M1 and three M2 cases, myeloid markers were present in two cases of M4, and both myeloid and monocytic markers were demonstrated in one case of AUL. Blast cells were negative for both myeloid and monocytic markers in most cases of AUL and M6. ALP-positive cells were increased distinctly (>10.0%) only in a small number of cats (15.4%) which included cases of M1, M2, M4. M6 and MDS. Prominent haematological abnormalities in most of the AML and MDS cases included moderate to severe thrombocytopenia, normocytic normochromic non-regenerative anaemia, normoblastaemia, leukocytosis accompanied by a left shift, and a variable number of circulating blast cells. Circulating blast cell counts of ⩾30.0% were seen in only 15.3% cats. Mean leukocyte counts were over 100 000/μl in most of the M5 and M4 cats and in an occasional M1 cat, whereas AUL cats generally had leukocyte counts within the normal range. Leukopenia was evident in slightly over half of the MDS-Er cats, in nearly a third of the M2 cats, and in a small number of cats in other categories. Monocytosis was most pronounced in M5 cats and prominent in M4 cats. Other abnormalities seen in a small number of cats included hyperproteinaernia or hypoproteinaemia, hyperfibrinogenaemia, elevated icterus index, and thrombocytosis.     

妇科养坤丸与骨髓间充质干细胞移植修复薄型子宫内膜

BACKGROUND: Studies have found that endometrial cells from bone marrow donors can be detected in the endometrium of female patients after bone marrow suppression.OBJECTIVE:To investigate the effect of Fukeyangkun pills combined with bone marrow mesenchymal stem cells (BMSCs) transplantation in the treatment of thin endometrium.METHODS: Thirty female rats at rutting period were randomized into control, model, Fukeyangkun pills, cell transplantation and combined group (n=6 per group). Rat models of thin endometrium were made in the latter five groups. Rats in the six groups were respectively subjected to routine feeding, tail vein injection of normal saline, tail vein injection of bone marrow mesenchymal stem cells (1 mL) at 6 hours and 10 days after modeling, intragastric administration of 5 mL/kg Fukeyangkun pill solution for continuous 20 days, or tail vein injection of bone marrow mesenchymal stem cells (1 mL) at 6 hours and 10 days after modeling plus intragastric administration of 10 mL/kg Fukeyangkun pill solution for continuous 20 days. At 21 days after modeling, hematoxylin-eosin staining was used to observe the morphological changes of the endometrical tissues and measure the endometrium thickness. The expression of cytokeratin and vimentin was determined by western blot assay.RESULTS AND CONCLUSION: Compared with the model group, the endometrium thickness and the expression of cytokeratin and vimentin (P < 0.05) were increased successively in the Fukeyangkun pills group, cell transplantation group, and combined group to different extents. Of these groups, the endometrium thickness and the expression of cytokeratin and vimentin in the combined group were the most close to normal levels. Our data demonstrate that bone marrow mesenchymal stem cell transplantation can induce regeneration of the endometrial cells and repair endometrial tissue. Furthermore, treatment of Fukeyangkun pills obviously augments the repair effect of bone marrow mesenchymal stem cell transplantation on thin endometrium.  中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

miR-31 promotes the proliferation and migration of bone marrow mesenchymal stem cells北大核心

BACKGROUND: Bone marrow mesenchymal stem cells have been widely used in the clinical treatment of neurodegenerative-related diseases, but their efficacy is reduced by low cell survival and migration rates at the site of injury. OBJECTIVE: To investigate whether miR-31 can enhance the migration and proliferation of bone marrow mesenchymal stem cells. METHODS: Bone marrow mesenchymal stem cells from C57BL/6 mice were cultured and identified, and the cells were divided into control, miR-31 agomir, and miR-31 antagomir groups. Bone marrow mesenchymal stem cells at passage 3 were inoculated in six-well plates (1×105/well). When the cells reached 50%-80% fusion, miR-31 agomir and miR-31 antagomir were added to the six-well plates after dilution with serum-free DMEM/F12. After 24 hours of transfection, the proliferation level of cells was analyzed by CCK-8 assay as well as the migration ability of cells was analyzed by Transwell assay. Protein expression of matrix metalloproteinase 2 and CXC chemokine receptor 4 was detected by western blot assay. RESULTS AND CONCLUSION: (1) miR-31 was successfully transfected with bone marrow mesenchymal stem cells without transfection reagents and emitted red fluorescence. (2) After transfection, the proliferation ability of cells in the miR-31 agomir group was enhanced compared with the control group, which increased proportionally with time (P < 0.05). Compared with the control group, miR-31 promoted the migratory ability of bone marrow mesenchymal stem cells in the miR-31 agomir group (P < 0.05) and also upregulated protein expression of matrix metalloproteinase 2 and CXC chemokine receptor 4 (P < 0.05). (3) The results indicated that miR-31 could improve the proliferation ability of bone marrow mesenchymal stem cells and promote the migration of bone marrow mesenchymal stem cells, which provides a basic study for efficient targeting of mesenchymal stem cell migration to the site of injury. © 2023, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

In vivo anti-tumor activity of murine hematopoietic stem cells expressing a p185HER2-specific chimeric T-cell receptor gene

We have confirmed efficient anti-tumor activities of the peripheral lymphocytes transduced with a p185HER2-specific chimeric T-cell receptor gene both in murine and in human in our previous studies. To further test the feasibility of chimeric T-cell receptor in a bone marrow transplantation model, we first, made two murine tumor cell lines: MT901 and MCA-205, to express human p185HER2 by retroviral gene transduction. Murine bone marrow cells were retrovirally transduced to express the chimeric T-cell receptor and gene-modified bone marrow cells were transplanted into lethally irradiated mouse. Six months post transplantation, p185HER2-positive tumor cells:MT-901/HER2 or MCA-205/ HER2 was subcutaneously or intravenously injected to make mouse models simulating primary breast cancer or pulmonary metastasis. The in vivo anti-tumor effects were monitored by the size of the subcutaneous tumor or counting the tumor nodules in the lungs after India ink staining. The size of the subcutaneous tumor was significantly inhibited and the number of pulmonary nodules were significantly decreased in mouse recipients transplanted with chimeric T-cell receptor modified bone marrow cells compared with the control group. Our results suggest the efficient in vivo anti-tumor activities of chimeric T-cell receptor gene modified bone marrow cells.     

Application of Stem Cells in Tissue Engineering

Stem cells have become an important source of seed cells for tissue engineering because they are relatively easy to expand in vitro and can be induced to differentiate into various cell types in vitro or in vivo. In the current stage, most stem cell researches focus on in vitro studies, including in vitro induction and phenotype characterization. Our center has made a great deal of effort in the in vivo study by using stem cells as seed cells for tissue construction. We have used bone marrow s…     

中药诱导骨髓间充质干细胞的定向分化：研究与进展

BACKGROUND: In recent years, in-depth studies that single Chinese herbs or extracts, compound traditional Chinese medicine and medicated serum are used to regulate the directional differentiation of bone marrow mesenchymal stem cells into myofibroblasts, chondrocytes, osteoblasts, myocardial cells and nerve cells, which have become a highlight in the tissue engineering research.OBJECTIVE: To review the latest progress in the directional differentiation of bone marrow mesenchymal stem cells induced by Chinese herbs or their extracts.METHODS: The first author searched the CNKI, Wanfang and PubMed databases using the keywords of “Chinese herb, directional differentiation, mesenchymal stem cells” in Chinese and English, respectively, to retrieve relevant articles published from January 2010 to January 2016. Repetitive articles or those with no originality were eliminated. Totally 99 articles were searched initially, and then 43 articles were included in result analysis.RESULTS AND CONCLUSION: As the strongest seed cells in the bone differentiation system, bone marrow mesenchymal stem cells have a wide range of directional differentiation potential, and highlight the important value in combination with Chinese herbs for clinical treatment of various refractory diseases, especially for treatment of metabolic bone diseases, bone defects, nonunion and delayed union, which is not only conducive to in-depth, multi-angle studies on effects and mechanisms of Chinese herbs, but also to clinical treatment of various refractory diseases using bone marrow mesenchymal stem cells.   中国组织工程研究杂志出版内容重点：干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程     

Interleukin 17-Producing γδ T Cells Increased in Patients with Active Pulmonary Tuberculosis

Although it has been known that γδ T cells may play an important role in the immune response to infection of Mycobacterium tuberculosis （M. tb）, the mechanisms by which the γδ T cells participate in the innate and/or acquired immunity to tuberculosis （TB） have not been full elucidated. In the present study, 27 patients with active pulmonary TB and 16 healthy donors （HD） were performed. We found that proportion of IL-17-producing cells among lymphocyte was similar between TB patients and HD, whereas the proportions of γδ T cells in IL-17-producing cells （59.2%） and IL-17-producing cells in γδ T cells （19.4%） in peripheral blood were markedly increased in TB patients when compared to those in HD （43.9% and 7.7%, respectively）. In addition, the proportions of IFN-T-producing γδ T cells in TB patients were obviously lower than that in HD. Upon re-stimulated with M. tb heat-treated antigen （M. tb-HAg） in vitro, fewer IL-17-producing γδ T cells were generated from HD and TB patients, whereas IFN-T-producing γδ T cells were increased in TB patients compared to that in HD. Our findings in TB patients and healthy human were consistent with other murine investigation that the IL-17- producing γδ T cells were main source of IL-17 in mouse model of BCG infection, suggesting that γδ T cells might be involved in the formation of tubercular granuloma in pulmonary TB patients, but need further identification.     

骨髓增生异常综合征患者临床特征分析

目的 探讨细胞形态学检查、流式细胞术、细胞遗传学对MDS诊断分型的作用。方法 以2016年WHO对MDS诊断分型标准为主要参考,回顾性分析安徽医科大学附属安徽省立医院2013年5月~2017年的12月收治住院的120例成人MDS患者的临床症状、血常规、骨髓细胞学、骨髓病理、免疫表型、细胞遗传学方面的特点。结果 120例MDS患者,根据2016年WHO分类,有2例（1.67%）患者符合MDS伴单系病态造血 (MDS-SLD);有27例（22.50%）患者符合MDS伴多系病态造血 (MDS-MLD),各有3例（2.50%）和4例（3.33%）患者符合MDS伴环状铁粒幼红细胞伴单系发育异常（MDS-RS-SLD）和MDS伴环状铁粒幼红细胞伴多系发育异常（MDS-RS-MLD）,各有 34例（28.33%）和43例（35.83%）是MDS-EB-1和MDS-EB-2;2例（1.67%）单纯5q-的MDS;有5例（4.17%）患者MDS未分类。结论 骨髓细胞形态学和外周血指标仍是MDS诊断的金标准,临床症状、血常规、骨髓细胞学、骨髓病理、免疫表型、细胞遗传学的综合考虑更有利于MDS的分型诊断,并对治疗、预后判断有重要指导价值。     

Increased angiogenesis in the bone marrow of HIV-positive patients with myelodysplasia

AIM: Little is known about the significance of angiogenesis in the bone marrow of HIV-positive patients with myelodysplastic features (MDF). However, this process has been associated with the pathogenesis of primary myelodysplastic syndromes (MDS). The aim of the study was to investigate angiogenesis in the bone marrow of HIV-positive patients. METHODS: Bone marrow biopsies from 28 HIV-positive patients were immunostained for factor VIII and the microvessel density (MVD) was quantitatively evaluated and compared with that of 32 biopsies from patients with primary MDS and to 18 control bone marrows from patients with no evidence of bone marrow disease. RESULTS: Bone marrow MVD in HIV-positive patients was similar to that of MDS. However, both groups revealed significantly higher MVD counts compared to those of control bone marrows (MDF vs controls P=0.022, MDS vs controls P=0.001). CONCLUSIONS: Bone marrow from HIV-positive patients with MDF reveals similar microvessel counts compared to those with primary MDS, although both differ significantly from that of control bone marrow. Elucidation of the mechanisms underlying bone marrow angiogenesis in HIV-positive patients, may provide further insights into the pathobiology of AIDS and might be of value for the development of new therapeutic strategies for this disease.     

Conventional and molecular cytogenetic findings of myelodysplastic syndrome patients

Abstract Myelodysplastic syndrome (MDS) involves myeloid cells of the bone marrow, which is important in progressive bone marrow insufficiency. Of all MDS patients, 40%–50% have at least one chromosomal rearrangement. Loss of specific chromosomal regions like 5q– and 7q– are usually the secondary cytogenetic abnormalities associated with MDS. In order to detect chromosome abnormalities associated with MDS, bone marrow samples from 26 patients diagnosed as MDS were obtained prior to chemotherapy. Both conventional cytogenetic analyses and fluorescence in situ hybridisation (FISH) methods were performed and locus–specific probes for 5q and 7q were used. Results obtained were compared. Twenty–one patients had normal karyotypes and four patients had abnormal karyotypes, while in one patient we could not obtain metaphases from cultures. Three patients with normal karyotypes revealed del (5q), two patients had del (7q) and one patient had monosomy (7). A total of 10 of 26 patients had chromosome changes visualised by either conventional or molecular cytogenetics (~38.5%). Our results show that both methods are important in diagnosis and follow up of MDS patients. When used together, conventional cytogenetics and FISH detect clinically significant chromosome abnormalities in MDS patients.     

High Incidence of Morphological Myelodysplasia and Apoptotic Bone Marrow Cells in Behçet’s Disease

Beh?et's disease (BD) is a systemic inflammatory disorder of unknown etiology, and rarely complicated with myelodysplastic syndrome (MDS). In the present study, we investigated the morphological myelodysplasia and apoptotic rate of bone marrow cells in 15 patients with BD in comparison with MDS patients. Morphological myelodysplasia of bone marrow cells was detected in 53.3% of BD, but none showed chromosomal abnormalities. The apoptotic rate in BD patients (26.1 +/- 8.4%) was significantly higher in normal controls (11.3 +/- 2.4%; p < 0.005) and significantly lower in patients with MDS (50.8 +/- 14.0%; p < 0.0001). These findings suggest that myelodysplasia in patients with BD is more frequent than expected, and possibly due to excess induction of apoptosis of bone marrow cells in BD. However, the rate of apoptotic bone marrow cells is lower than MDS, which may explain the slight peripheral cytopenia in BD, distinct from that in MDS.     

Expression of Toll-like receptor 9 in bone marrow cells of myelodysplastic syndromes is down-regulated during transformation to overt leukemia

Toll-like receptors (TLRs) play a crucial role in the host defense against invading microorganisms by recognizing pathogen-associated molecular patterns. Recently, a number of endogenous molecules have been reported to be ligands of TLRs. Some of these molecules are known to be expressed in cancer tissue and activate intracellular signal pathways via TLRs during cancer progression. Thus, in the present study, we analyzed the expression dynamics of TLRs in the bone marrow of myelodysplastic syndromes (MDS) during the course of transformation to overt leukemia (OL) using real-time RT-PCR. MDS bone marrow cells at the time of initial diagnosis tended to express higher levels of TLR2, TLR4 and TLR9 than control bone marrow cells. Among these TLRs, TLR9 exhibited a significant decrease of expression at the time of transformation to OL. The expression of TLR9 and TNF-α showed significant correlation in bone marrow cells from patients with MDS and OL. Immunohistochemically, TLR2 was mostly localized to neutrophils of the control and MDS bone marrow. TLR4 was observed in a subset of neutrophils and a few mononuclear cells in control and MDS bone marrow. In addition, TLR4 was weakly expressed in nearly half of immature myeloid cells of MDS cases. TLR9 was mainly localized to neutrophils in the control and RA bone marrow and strongly expressed in the immature myeloid cells of RAEB cases, although the blastic cells of OL cases did not express TLR9. Bone marrow cells in MDS exhibit frequent apoptosis, while OL cells are prone to be immortal. Thus, TLR9 might be associated with regulation of apoptotic/proliferative signals via TNF-α in the MDS bone marrow.     

流式细胞术CD34+细胞计数在骨髓增生异常综合征分型诊断中的作用

为探讨流式细胞术(FCM)CD34+细胞计数在骨髓增生异常综合征(MDS)分型诊断中的应用价值.采用多参数FCM设门技术检测MDS患者骨髓CD34+细胞计数,与形态学分型诊断比较.结果显示:对照组和MDS组形态学原始细胞计数分别为0.43±0.64%和2.50±3.68%,FCM CD34+细胞计数分别为0.45±0....     

p53 expression in myeloid cells of myelodysplastic syndromes. Association with evolution of overt leukemia.

To assess p53 expression in the hematopoietic cells of the bone marrow in premalignant as well as malignant conditions, we examined immunohistochemically bone marrow biopsies from patients with myelodysplastic syndromes (MDS, n = 51), acute myeloid leukemia (n = 42) and as a nonneoplastic condition, aplastic anemia (n = 20) and samples from individuals who had no hematological disorder (control, n = 12). Nuclear accumulation of p53 protein was found in seven of 51 patients with MDS (14%) and two of 42 acute myeloid leukemia patients (5%), whereas patients with aplastic anemia and control subjects were uniformly negative for p53 protein. In the bone marrow of patient with MDS, p53-positive cells constituted about 5 to 30% of the total bone marrow cells. Two-color immunohistochemical analysis revealed that the p53-positive cells were also positive for the myeloid cell marker. Half of the MDS cases that evolved to overt leukemia (seven of 14) exhibited positive p53 reaction in the bone marrow at the time of initial diagnosis. This frequency (50%) was significantly higher than that in de novo acute myeloid leukemia cases. All of the seven MDS cases that exhibited p53 expression at the time of initial diagnosis developed overt leukemia later, and p53 expression was maintained throughout the progression of MDS. The results suggest that p53 mutations that occur in the myeloid cells in MDS may confer a growth advantage to these cells resulting in the progression to overt leukemia. Thus, immunohistochemical examination for p53 is very useful for predicting the evolution to overt leukemia from MDS.     

The treatment of myelodysplastic syndromes

The available data fail to support a standard therapy for MDS. Any therapy should therefore, include participation in a well designed clinical trial. The MDS include patients with a variety of prognoses. Since most studies show that death from infection and bleeding are more likely than progression to frank leukaemia, attention to supportive care is crucial for all patients with MDS. Some patients with MDS may be successfully supported with transfusions and observation for prolonged periods. Patients with significant comorbid disease or patients without increased marrow myeloblasts are good candidates for this conservative approach. Conversely, young patients have a better likelihood of benefit from aggressive therapy, and intensive chemotherapy or allogenic bone marrow transplantation should be considered. Patients with preleukaemia related to prior cytotoxic therapy are another poor prognosis group for whom aggressive therapy may be the best alternative. Therapy with low-dose ara-C or other differentiating agents should be considered investigational and unproven until comparative trials can demonstrate a definitive survival advantage. In addition to comparative trials, innovative clinical studies are needed to address differentiation as an in vivo mechanism of action and its importance in MDS therapy.     

骨髓活检与涂片联检对诊断骨髓增生异常综合征的临床意义

目的探讨骨髓活检切片与骨髓穿刺涂片联检对诊断骨髓增生异常综合征(myelodysplastic syndrome,MDS)的临床意义。方法对122例MDS患者采用骨髓抽吸与活检标本同步法取材,同步观察其涂片和切片。结果骨髓活检切片MDS诊断符合率明显高于骨髓涂片,骨髓增生活跃程度、骨髓涂片的明显活跃与切片差异均有统计学意义(P<0.05)。粒系病态造血骨髓切片检出率高于涂片(P<0.05),红系病态造血骨髓涂片检出率高于切片(P<0.05),巨核系病态造血检出率骨髓切片与涂片差异无统计学意义。结论骨髓涂片和活检切片在MDS的诊断和分型中各有优点、两者相互补充,同步观察更有利于提高MDS诊断和分型的准确性。     

Marrow fibrosis as a risk factor for posttransplantation outcome in patients with advanced myelodysplastic syndrome or acute myeloid leukemia with multilineage dysplasia.

Marrow fibrosis is considered a poor prognostic factor in patients with myelodysplastic syndrome (MDS). The affect of fibrosis on outcomes after hematopoietic cell transplantation (HCT) in patients with MDS has not been examined. We performed a retrospective analysis in 471 patients with MDS or acute myeloid leukemia with multilineage dysplasia arising from MDS, 113 with and 358 without marrow fibrosis, who received myeloablative allogeneic HCT. Post-HCT follow-up was 0.3-10 years (median, 3.6 years) for patients with, and 0.6-12 years (median, 5 years) for patients without fibrosis. Engraftment was significantly delayed in patients with fibrosis (hazard ratio [HR] = 0.4; P < .001). Overall, there were no significant differences in overall survival (OS), relapse-free survival (RFS), and nonrelapse mortality (NRM) between patients with and without fibrosis. However, among patients with advanced disease (int-2 or high-risk disease by the International Prognostic Scoring System), OS (P = .03), RFS (P = .04), and NRM (P = .04) were inferior when marrow fibrosis was present. Given that marrow fibrosis is a poor prognostic factor for patients with MDS, and that it does not appear to affect outcome of transplantation in patients with earlier-stage disease but has a negative impact on outcome for patients with advanced disease, patients with earlier-stage MDS and marrow fibrosis might be considered for HCT earlier than their disease stage would normally dictate.