Expression of Insulin-like Growth Factor Recepter Type I in CD34 Cells of Patients with Myelodysplastic Syndromes / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the expression level of insulin-like growth facter (IGF-IR) in CD34 cells of patients with myelodysplastic syndromes(MDS).</p><p><b>METHODS</b>Flow cytometry was used to detect the expression of IGF-IR in the CD34 cells of 100 MDS patients and 18 normal controls.</p><p><b>RESULTS</b>The average IGF-IR expression level in the CD34 cells of 100 MDS patients (41.0±28.1)% was statistically and significantly elevated in comparison with the corresponding level in normal controls(4.3±1.8)%,(P<0.0001). The average expression level of 22 cases in high-risk groups was very significantly increased, compared with that in 78 cases of low-risk groups[(66.5±27.8)% vs (34.5%±24.9)%](P<0.0001), and the average expression level in 23 patients with chromosome abnormality was very significantly increased in comparison with that in rest 77 patients [(56.0±30.9)% vs (36.9%±26.2)%](P<0.01).</p><p><b>CONCLUSION</b>The over-expression of IGF-IR in CD34 cells of MDS patients suggests that the IGF-IR may involve in the origin, occurrence and progress. The average IGF-IR expression level is markedly elevated in high-risk groups and the patients who showed chromosome abnormality, this trend revealed that IGF-IR correlates with malignant clonal proliferation in MDS patients, thus providing a basis for their prognosis and outcome evaluation.</p>

Study on phenotypic and cytogenetic characteristics of bone marrow mesenchymal stem cells in myelodysplastic syndromes / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate phenotype, cell differentiation and cytogenetic properties of bone marrow (BM) mesenchymal stem cells (MSC) separated from the myelodysplastic syndrome (MDS) patients. And to analyze cytogenetic aberration of MSC derived from MDS (MDS-MSC) and its mechanism in pathogenesis of MDS.</p><p><b>METHODS</b>Adherent MSC from both myelodysplastic (n = 22) and normal (n = 7) marrow were obtained by a stromal culture procedure. Morphological features were observed by optical microscope. The cell-surface antigens were performed by flow cytometer(FCM). Adipogenic and osteogenic differentiation potential of MSC were identified under specific induction conditions. Standard cytogenetic analysis of both hematopoietic cells and MSC were performed by trypsin-Giemsa (GTG) banding. The karyotype analysis DNA content was determined by FCM to verify the results.</p><p><b>RESULTS</b>The morphology of MDS-MSC was typical slender spindle-shaped cells, MSC obtained from MDS patients had a MSC immunophenotype, lacked the expression of hematopoietic antigens-CD34, CD45 and expressed MSC markers, such as CD73, CD90, and CD105. MDS-MSC layers showed the capability to differentiate towards adipocytes, chondrocytes and osteoblasts. Cytogenetic aberrations were observed in MSC from 14 (64%) MDS patients, usually involve the loss of chromosomal material (92%), and the clonal loss (7 cases, 50%). Two cases of structural aberrations were also detected. Abnormal karyotypes in MSC were still more frequently identified in abnormal hematopoietic cells group (12 out of 13, 92% vs 3 out of 9, 33%, P < 0.05). There were not exactly the same type of chromosomal aberrations between hematopoietic cells and MSC, but different type of the aberrations in the same chromosome were involved.</p><p><b>CONCLUSION</b>MDS-MSC retains the phenotyping characteristics and differentiated function of normal MSC, but has different type of chromosomal abnormalities. A high proportion of loss of chromosomal may be a marker of chromosomal instability of MDS-MSC. Detection of abnormalities in MDS-MSC suggests enhanced genetic susceptibility of these cells in MDS. This may indicate potential involvement of MSC in the pathophysiology of MDS.</p>

Comparison of bone marrow biopsy and smear efficacy in patients with multiple myeloma / 中国实验血液学杂志

This study was aimed to explore the significance of the bone marrow biopsy for the diagnosis of multiple myeloma. Bone marrow smears and bone marrow biopsy originated from 279 cases of multiple myeloma were detected and compared in term of bone marrow hyperplasia, bone marrow plasma cell infiltration, proliferation mode, pathological changes in the bone marrow stroma and myelofibrosis. The results indicated that the levels of proliferation in bone marrow biopsy was significantly higher than that in bone marrow smears. Plasma cell proliferation mode in bone marrow biopsy was not completely consistent with the proportion of plasma cells in bone marrow smears. The myelofibrosis level displayed influence on the consistency of the proliferation between bone marrow smears and biopsies. It is concluded that as compared with bone marrow smears the bone marrow biopsy can more accurately reflect the levels of bone marrow hyperplasia and bone marrow plasma cell infiltration, proliferation mode and so on. Bone marrow biopsy is valuable for multiple myeloma diagnosis.

Cytogenetic study of autosomal monosomies among myelodysplastic syndrome patients / 中国实验血液学杂志

Monosomic karyotype (MK) has recently been associated with poor prognosis of myelodysplastic syndromes (MDS). The objective of the current study was to investigate the prevalence and spectrum of autosomal monosomies in an unselected cohort of patients with known or suspected MDS by using retrospective analysis. The results showed that bone marrow cytogenetic studies (1532 cases) were performed between 2004 and 2012, and an abnormal karyotype was found in 538 cases (35.1%). In the 538 cases, 202 (37.5%) cases had autosomal monosomies including sole (n = 47, 23.3%), part of two (n = 33, 21.3%) or more (n = 122, 78.7%) anomalies. Almost all 22 autosomes were involved, but monosomy 7 was by far the most frequent, constituting 66.1% of all isolated monosomies and the highest fraction of those with two or more abnormalities. Other recurrent sole monosomies included chromosomes 20 (15.0%) and 13 (8.5%). Monosomy 13 (12.5%), 18 (8.3%), 20 (6.3%), 17 (7.3%), 21 (5.2%), 5 (5.2%) and 12 (5.2%) were also recurrent in the setting of 3 abnormalities. Bone marrow histology and clinical information were reviewed in all cases with isolated monosomy; associated clinical phenotypes were found in RCMD (n = 20, 13 were -7), RAEB (n = 12, 11 were -7), RA (n = 9, 3 were -7) and chronic myelomonocytic leukemia (CMML, n = 6, 4 were -7) cases. Sole monosomy 20 (n = 7, RA 3 case and RCMD 4 cases) was not detected in RAEB or CMML cases. It is concluded that the presence of at least 1 autosomal monosomy was documented in approximately 37.5% of all abnormal cases, which has potential impact on a more than trivial fraction of patients with MDS. The preponderance of monosomy 7 implicates a pathogenetic role for haploinsufficiency of genes associated with chromosome 7. The rarity of sole monosomy involving other chromosomes other than 7, 20, and 13 suggests that haploinsufficiency involving entire chromosomes is detrimental to cell survival, unless their effect is overcome by the presence of other genetic changes that are often associated with additional chromosomal abnormalities. The observation is consistent with the usually favorable prognostic profile associated with sole monosomy 20.

The type I insulin-like growth factor receptor highly expressed in clonal cells of myelodysplastic syndromes / 中华血液学杂志

<p><b>OBJECTIVE</b>To probe the expression level of insulin-like growth factor-I receptor (IGF-IR) in malignant clone cells of myelodysplastic syndromes (MDS).</p><p><b>METHOD</b>The combination of fluorescence in situ hybridization (FISH) and immunochemistry (alkaline phosphatase anti-alkaline phosphatase, APAAP) was used to detect the expression of IGF-IR in the bone marrow cells of 40 MDS patients with abnormal karyotypes.</p><p><b>RESULTS</b>The average IGF-IR expression level on the clone cells \[(84.5 ± 14.2)%\] from the MDS cases was markedly elevated compared to the corresponding level on normal cells \[(11.4 ± 12.1)%\]. And the percentages of malignant clone cells in all 40 MDS cases were significantly correlated with the relevant percentages of IGF-IR positive nucleated cells (r = 0.929, P < 0.01).</p><p><b>CONCLUSIONS</b>IGF-IR might be taken as a marker of clone cells in MDS for its trait to malignant proliferation.</p>

Cytogenetic abnormalities in bone marrow mesenchymal stem cells from patients with myelodysplastic syndrome / 中国实验血液学杂志

This study was aimed to investigate the cytogenetic characteristics of hematopoietic cells (HC) and bone marrow mesenchymal stoma cells (BMMSC) isolated from patients with myelodysplastic syndrome (MDS) and healthy individuals as normal controls, and to clarify whether HC and BMMSC are simultaneously involved and participate in pathogenesis and development of MDS. Both marrows of 22 newly diagnosed patients with MDS and 7 healthy individuals were collected; BMMSC were isolated and amplified by using established culture system, as well as were identified according to morphologic features and surface antigens detected by flow cytometry; the characteristics of BMMSC from MDS patients were analyzed; the BMMSC karyotyping analysis of MDS patients was performed by banding of HC and BMMSC with pancreatin-Giemsa technique (GTG) and in accordance with ISCN (2005) requirements; the cytogenetic characteristics of HC and BMMSC were compared. The results showed that in vitro culture system for isolation and amplification was successfully established. The light microscopy and flow cytometry confirmed that BMMSC possessed characteristics showing long and thin spindle form and expressing CD29, CD73, CD90 antigens, and unexpressing CD34, CD45 antigens. In BMMSC of 14 MDS patients (64%), the cytogenetic abnormalities were found usually involving the loss of chromosomal material (92%), among which clonal loss was observed in 7 cases (50%). The detection indicated a random loss of chromosomal material in significant proportion of BMMSC. A high proportion of chromosomal material random loss may be a marker of chromosomal instability in BMMSC of MDS patients, the detection also showed that completely consistent aberration types did not exist between HC and BMMSC. The aberrations were observed in 3 cases of MDS with normal karyotype of HC, its aberration rate (33%) was obviously lower than that in MDS patients with abnormal karyotypes (92%). It is concluded that the cytogenetic abnormalities exist in BMMSC of MDS patients, the unbalanced aberration of chromosomal materials may be a genetic instability marker of BMMSC. The difference of aberration types in BMMSC from HC suggests that genetic susceptibility of BMMSC and HC is similar, but no completely identical, which indicates the potential involvement of BMMSC in pathogenesis of MDS. Studying this potential role of BMMSC can be helpful to further understanding of MDS biological characteristics and provide the new approaches for diagnosis and therapy of MDS.

Expression of insulin-like growth factor receptor type I in marrow nucleated cells from hematologic malignancies and its anti-apoptotic effect / 中国实验血液学杂志

To explore the expression of insulin-like growth factor receptor type I (IGF-IR) and its relationship to apoptosis in hematopoietic cells of MDS and AML marrow, bone marrow nucleated cells from 16 patients with myelodysplastic syndrome (MDS) and 16 patients with acute myeloid leukemia (AML) were collected for analysis, respectively. Another 16 normal donors' marrow samples were taken as controls. Immunocytochemical method (APAAP) and TdT-mediated dUTP nick end labeling (TUNEL) fluorescence were used simultaneously on cytospins of nucleated cells from these patients. Then, the ratios of IGF-IR positive cells and apoptosis cells in all nucleated cells were counted separately. The results showed that (1) there was a higher IGF-IR expression rate (56.8 +/- 14.3)% in nucleated cells of MDS marrow than that in normal marrow (40.4 +/- 9.6)% (P < 0.01). Also IGF-IR positive rate in AML marrow (86.8 +/- 13.8)% was significantly higher than that in normal marrow (P < 0.01). Furthermore, IGF-IR had higher expression in AML marrow when compared to MDS marrow (P < 0.01); (2) apoptosis in nucleated cells of MDS marrow (5.4 +/- 3.0)% was significantly higher than that in normal marrow (1.2 +/- 0.9)% (P < 0.01) and AML marrow (0.3 +/- 0.4)% (P < 0.01), while there was less apoptosis in AML marrow than that in normal marrow (P < 0.01); (3) apoptosis occurred mainly in IGF-IR negative cells (9.0 +/- 4.8)% and less in IGF-IR positive cells (1.4 +/- 2.4)% (P < 0.01). IGF-IR expression showed negative correlation with apoptosis (r = -0.852, P < 0.01); (4) IGF-IR of MDS nucleated cells in RAEB/RAEB-t/CMML expressed higher than that in RA/RAS (64.1 +/- 3.2% vs 53.5 +/- 16.2%) subgroup, although no significant difference was found (P > 0.05); and apoptosis in RAEB/RAEB-t/CMML subgroup was lower than that in RA/RAS cases (3.1 +/- 2.1% vs 6.4 +/- 2.8%) (P < 0.05); (5) IGF-IR positive rate in nucleated cells of MDS and AML marrow showed positive correlation with blast rate (r = 0.677; P < 0.01). It is concluded that there is overexpression of IGF-IR in marrow nucleated cells in MDS and AML cases. And it seems that the overexpression of IGF-IR may suggest some malignant proliferation tendency and suppress cell apoptosis through some mechanism in these malignant hematologic ailments. So, anti-IGF-IR will become a new approach for therapy of MDS and AML.

Expression of intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 in salivary glands of patients with Sj(?)gren's syndrome / 中华风湿病学杂志

Objective To explore the role of intercellular adhesion molecule-1(ICAM-1)and lym- phocyte function-associated antigen-I(LFA-1)in the pathogenesis of Sjgren's syndrome(SS)and provide a theoretical basis for clinical therapy.Methods Immunohistochemical method was used to detect these two cellular adhesion molecules in labial salivary glands of primary Sjgren's syndrome patients and 15 healthy controls.Semiquantitative analysis was performed by image analysis software.Results①In salivary gland samples,the expression of both ICAM-1 and LFA-1 was significantly higher compared to that of controls(P