Activin receptor-like kinase 1 and its roles in angiogenesis / 中国病理生理杂志

Activin receptor-like kinase (ALK) 1 is a transforming growth factor-β/bone morphogenetic pro-teins superfamily type Ⅰ receptor, predominantly expressed in active endothelial cells. ALK1 has been shown to play a piv-otal role in regulating angiogenesis, which is involved in vascular formation during embryonic and early postnatal develop-ment and angiogenesis-related diseases, such as cardiovascular disorders and tumor. Understanding the exact function of ALK1 in angiogenesis will provide theoretical basis for anti-angiogenic strategy of ALK1 inhibition. In the present study, we briefly recapitulate ALK1 signaling pathway and its role in blood vessel formation and pathological neovascularization.

Human Umbilical Cord-derived Mesenchymal Stem Cells Secrete Interleukin-6 to Influence Differentiation of Leukemic Cells / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the effect of human umbilical cord-derived mesenchymal stem cells (UC-MSC) on the differentiation of leukemic cells.</p><p><b>METHODS</b>The co-culture system of UC-MSC with acute promyelocytic leukemic cell line NB4 cells was constructed in vitro,and the differentiation status of the leukemic cells was assessed by cell morphology,nitroblue tetrazolium reduction test,and cell surface differentiation marker CD11b.</p><p><b>RESULTS</b>UC-MSC induced the granulocytic differentiation of NB4 cells. When UC-MSC and a small dose of all-trans retinoic acid were applied together,the differentiation-inducing effect was enhanced in an additive manner. Interleukin (IL)-6Ra neutralization attenuated differentiation and exogenous IL-6-induced differentiation of leukemic cells.</p><p><b>CONCLUSION</b>UC-MSC can promotd granulocytic differentiation of acute promyelocytic leukemia cells by way of IL-6 and presented additive effect when combined with a small dose of all-trans retinoic acid.</p>

Adipogenic potentials of mesenchymal stem cells from human bone marrow, umbilical cord and adipose tissue are different / 中国实验血液学杂志

Mesenchymal stem cells (MSCs) could be obtained from many sources, and there are differences between them. This study was purposed to compare and analyze the basic biological characteristics of umbilical cord, adipose tissue-and bone marrow-derived MSC (UC-MSCs, AD-MSCs and BM-MSCs). The MSCs were isolated from umbilical cord, adipose tissue and bone marrow were cultured; the morphology of UC-MSCs, AD-MSCs and BM-MSCs was observed by using microscopy; the immunophenotype, differentiation potential and expression of peroxisome proliferation-activated receptor-γ (PPAR-γ) mRNA were detected by using flow cytometry, differentiation test (von kossais and 0:1 red O staining) and quantitative fluorescent PCR, respectively. The results showed that the UC-MSCs, AD-MSCs and BM-MSCs displayed similar morphology under confocal microscope after being stained with rhodamine phalloidin and DAPL. The immunophenotypes of these three originated cells conform to coincide with identification criterion for MSCs, and showed similar expression level. During adipogenic induction the adipogenic potential of these MSCs was different, AD-MSCs exhibited the highest adipogenic potential, UC-MSCs displayed the lowest, while potential of BM-MSCs get between; however, the osteogenic differentiation potential of UC-MSCs, AD-MSCs and BM-MSCs was similar. The PCR detection showed that the expression level of PPAR-γ mRNA was the highest in AD-MSCs and the lowest in UC-MSCs, while expression level in BM-MSCs get between, these results were identical with the adipogenic potential, suggest that the difference of adipogenic potential in 3 kinds of MSCs was associated with basic expression level of PPAR-γ mRNA. It is concluded that UC-MSCs, AD-MSCs and BM-MSCs exhibit similar morphology, the immunophenotypes of these MSCs coincide with identification criterion for MSCs, the osteogenic potential of these MSCs is similar, while the adipogenic potential and the expression level of PPAR-γ mRNA are different. The difference-associated mechanisms need to further study.

Additional karyotypic abnormalities analysis in patients with hematological malignancies post-allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the karyotype stability in hematological malignancies patients before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its prognostic significance of monitoring.</p><p><b>METHODS</b>The karyotypes and clinical data of 21 patients with hematological malignancies at the initial diagnosis and at relapse after allo-HSCT were retrospectively reviewed. Chromosome analysis was performed by standard 24 h-cultured method and R banding.</p><p><b>RESULTS</b>Karyotypes at the initial diagnosis and at relapse after allo-HSCT were different in 11 patients (52.38%), including chromosome 1, 3, 6, 12, 17, 21. Numberical abnormalities and structural chromosomal abnormalities always occurs together. The median survival time of relapse of the patients with karyotype changes was significantly shorter than that of patients without a karyotype change (79 d vs 522 d, P = 0.027), and that of the patients with trisomy 6 was also significantly shorter than that of the patients without trisomy 6 (9 d vs 275 d, P = 0.005).</p><p><b>CONCLUSION</b>Karyotype changes after relapse are associated with the prognosis of allo-HSCT.</p>

Clinical and laboratory investigation of patients with hematologic malignancies harboring der(1;7)(q10;p10) / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the clinical and laboratory characteristics of patients with various hematological malignancies harboring der(1;7)(q10;p10).</p><p><b>METHODS</b>Bone marrow samples were collected and undergone short-time unstimulated culture and R-banding, and karyotyped by conventional cytogenetic assay (CCA). Megalokaryocytes were detected by streptavidin-AKP (SAP). Retrospective analyses including the clinical and laboratory data were performed.</p><p><b>RESULTS</b>Nineteen of the 21 patients were male. Most of the patients are of older age. Thirteen cases (61.9%) were der(1;7)(q10;p10) without additional aberrations, 8(38.1%) patients had additional aberrations. Sixteen out of the 18 cases (88.9%) who underwent SAP analysis had diminutive megalokaryocyte, and lymphoid megalokaryocyte was found in 10 cases (55.6%). The der(1;7) patients manifested poor response to treatment.</p><p><b>CONCLUSION</b>The der(1;7) patients demonstrated distinct male predominance, older age at diagnosis, and some clinically distinctive features. These patients showed poor prognosis. The cytogenetic abnormality, i.e., der(1;7)(q10;p10), can be used as a prognostic indicator.</p>

Identification of complex chromosomal aberrations in acute leukemia by using conventional cytogenetics combined with multiplex fluorescence in situ hybridization / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the value of multiplex fluorescence in situ hybridization (M-FISH) technique in the detection of the complex chromosomal aberrations (CCAs) and marker chromosomes in acute leukemia (AL).</p><p><b>METHODS</b>M-FISH was performed in 11 AL patients with R-banding CCAs or marker chromosomes to define the unrecognized chromosomal aberrations and the constitution of marker chromosomes, and to identify small and cryptic translocations.</p><p><b>RESULTS</b>In the 11 AL cases studied, 27 numerical and 41 structural chromosomal abnormalities were detected by conventional cytogenetics (CC), among which 3 chromosomal gains and 9 chromosomal losses as well as 12 structural abnormalities were confirmed by M-FISH, and another 15 chromosomal losses were revised by M-FISH as derivative chromosomes. M-FISH detected 3 additional chromosomal gains that were undetected by CC. The other 29 structural abnormalities including 17 marker chromosomes were characterized by M-FISH. A total of 33 structural abnormalities were detected by M-FISH, in which 6 were unreported before, i.e. t(5q-;16)(? q14;q24), der(9)(Y::9::Y::9), der(7) (7::8::9), ins(20;21), der(11) (11::21::20) and der(3)t(3p-;13)(3p-;q21), most of which resulted from unbalanced translocations. Almost all chromosomes were involved in CCAs, the more common ones were chromosome 17, 5, 7, 15, 11 in AML and 8, 9, 14, 22 in ALL.</p><p><b>CONCLUSION</b>Combining M-FISH with CC can raise resolution of the latter, which justifies its clinical application for the detection of CCAs and marker chromosomes.</p>

Study on clonal evolution of monosomy 7 in patients with aplastic anemia by interphase- fluorescence in situ hybridization / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the clonal evolution of monosomy 7 in patients with aplastic anemia (AA).</p><p><b>METHODS</b>Monosomy 7 (-7) in 81 AA patients with normal karyotype at diagnosis and 46 AA treated with immunosuppressive therapy (IST) and more than 6 months of recombinant human granulocyte colony-stimulating factor (rhuG-CSF) were detected by interphase- fluorescence in situ hybridization (FISH) retrospectively.</p><p><b>RESULTS</b>There were 5.4% - 7.6% of -7 cells in 11 (13.6%) of 81 patients at diagnosis, the survival and response rate to IST in -7 positive patients did not differ significantly from that in -7 negative patients (P = 0.481, 0.865); -7 cells disappeared after IST in all of the 11 patients including 5 received long-term rhuG-CSF therapy, and none of them evolved to myelodysplastic syndromes/acute myeloid leukemia (MDS/AML) at a median follow-up of 44 months. Serial assessments of -7 clones were performed in 46 patients, none of whom detected -7 clones 3-6 months after IST, but -7 recurrence in 5 patients 12 - 15 months after IST. At a median follow-up of 48 months, FISH identified 6 patients with -7 clones while the conventional cytogenetic analysis (CCA) recognized in 5. Moreover, the first demonstration of -7 by FISH was 3 - 18 months earlier than that by CCA. All of the 6 patients with FISH detected -7 evolved to MDS/AML with -7 and four of them were retrospectively analysed for in samples at -7 diagnosis of AA, but none of them was positive.</p><p><b>CONCLUSIONS</b>Monosomy 7 exists in a part of AA patients, but the preexisting -7 cells seems neither associated with fatality nor evolvation to MDS/AML. rhuG-CSF might facilitate the expansion of -7 clones; It is necessary to monitor -7 in AA, especially when received long-term rhuG-CSF therapy.</p>

Detection of bcr/abl fusion gene by dual color-dual fusion fluorescence in situ hybridization / 中国实验血液学杂志

This study was aimed to investigate the sensitivity and clinical application of interphase-dual-color and dual-fusion fluorescence in situ hybridization (DC-DF-FISH). The bcr/abl fusion gene was detected by FISH with dual-color and dual-fusion bcr/abl DNA probe in interphase cells of bone marrow from 1295 specimens. Retrospective analysis for the cases was performed by the means of conventional cytogenetic analysis (CCA) and FISH. The results indicated that in 1295 specimens from 539 patients, 456 specimens were positive involved in 310 patients, the karyotypes of 18 patients were normal, 5 patients failed to karyotyping analysis. About 75.5% (234/310) of positive patients displayed the typical DC-DF-FISH signal pattern, 76 patients showed atypical DC-DF-FISH signal patterns, 66 cases out of which showed variant signal, 16 patients displayed typical variant signals (1Y2G2R), 50 patients displayed deletion ABL and/or BCR signal. In 213 patients, the negative rate was 60% (128/213) after the treatment, 12 patients were sometimes negative and sometimes positive during the process of the treatment. It is concluded that DC-DF-FISH can be used to detect karyotypes with masked or variant Ph, gene deletion and minor residual disease (MRD) in process of treatment. The dual-color FISH technique is a much more sensitive and accurate tool for monitoring MRD and monitoring relapse, which is a necessary supplement to CCA.

A comparative cytogenetic analysis in large scale between adult and childhood patients with acute lymphoblastic leukemia / 中国实验血液学杂志

This study was purposed to comparatively analyze the cytogenetic characteristics between 566 cases of adult acute lymphoblastic leukemia (aALL) and 586 cases of childhood acute lymphoblastic leukemia (cALL). The cytogenetic analysis of all the patients was performed, and the FISH detection for partial patients was carried out. The result showed that the difference of chromosome abnormality between cALL and aALL was statistically significant. The percentage of abnormal karyotypes in aALL was 62.0%, including mainly t(9;22)(q34;q11), hypodiploidy, hyperdiploidy (47 - 50), abn(6q), abn(9p) and -7, most of which conferring an unfavorable prognosis. The percentage of abnormal karyotypes in cALL was 39.2%, composed mainly of high hyperdiploidy, hypodiploidy, TEL/AML1(+), +8, hyperdiploidy (47 - 50) and +21, etc, most of which conferring a favorable prognosis. The incidences of abnormal karyotypes, total hypodiploidy, total hyperdiploidy (47 - 50), t(9;22)(q34;q11), -7, abn(7q), abn(14q32) and +Ph in aALL were significantly higher than those of cALL (p < 0.05), whereas the incidences of normal karyotype (N), high hyperdiploidy, +8, +21*2 and TEL/AML1(+) in cALL were significantly higher than those of aALL (p < 0.05). 20.5% of aALL were Ph+ aALL, with 63.8% of which being with additional abnormalities, composed mainly of +Ph, -7, i (9q+), 9p-, +8, +21, +X, 6q-, abn(14q32) and +14. In contrast, only 4.4% of cALL were Ph+ aALL, with 42.3% of which being with additional abnormalities, including mainly abn(9p), abn(7p), -7, 17p- and +21. It is concluded that almost every chromosome is involved in the numerical and structural abnormalities and complex karyotypes are common. The significant difference of chromosome abnormality exists between aALL and cALL.

Clinical and laboratory investigation of hematological malignancy patients carrying 3q21q26 rearrangement / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the clinical and laboratory characteristics of various hematopoietic malignant patients with t(3;3)(q21;q26) or inv(3) (q21q26).</p><p><b>METHODS</b>Bone marrow samples were collected at presentation, prepared by short-time unstimulated culture and R-binding, and karyotyped by conventional cytogenetical assay (CCA); megalokaryocytes were detected by Streptavidin-AKP (SAP); immunotype of the leukemia cells was tested by flow cytometric anylysis of surface antigens (FACS).</p><p><b>RESULTS</b>All of the 9 hematopoietic malignant patients with t(3;3)(q21;q26) or inv(3) (q21q26) manifested myelodysplasia and poor treatment response. One of them relapsed shortly after allogenic hemotopoietic stem cell transplantation (allo-HSCT).</p><p><b>CONCLUSION</b>Patients with 3q21q26 rearrangement can be found in various hematopoietic malignances and demonstrate an unique entity. These patients show poor treatment response and have extremely poor prognosis.</p>

Clinical and laboratory study of a complex translocation t (6; 21; 8) (p22; q22; q22) in two patients with acute myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical and laboratory characteristics of a complex translocation t (6; 21; 8) (p22; q22; q22) in two patients with acute myeloid leukemia.</p><p><b>METHODS</b>Bone marrow (BM) samples were collected at presentation, prepared by short-term (24 hours) unstimulated culture and R-binding, for conventional cytogenetic assay (CCA). The complex translocation was assayed by fluorescence in situ hybridization (FISH) with a dual-color AML1/ETO-specific probe. AML1/ETO chimeric transcript was detected by reverse transcription polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>In both cases CCA demonstrated a complex translocation, t (6; 8; 21) (p22; q22; q22), which was confirmed by interphase and metaphase FISH and AML1/ETO fusion transcript was detected by RT-PCR. Both the two patients were diagnosed as AML-M(2), but with different immunophenotype and therapeutic outcome.</p><p><b>CONCLUSION</b>The t (6; 21; 8) (p22; q22; q22) is a rare variant of complex translocation of t (8; 21) (q22; q22). More such cases are needed for elucidating its clinical features and prognosis.</p>

Conventional cytogenetics and fluorescence in situ hybridization as methods for detecting MLL gene rearrangements in leukemia / 中国实验血液学杂志

This study was aimed to compare the values of conventional cytogenetics (CC), interphase FISH and sequential R-banding and FISH analysis as methods for detecting MLL gene rearrangements. 37 acute leukemia patients were studied by CC and interphase FISH. The results showed that among them, 10 cases were 11q23(+)/MLL(+), 2 cases were 11q23(-)/MLL(+) (5.4%), 3 cases were 111q23(+)/MLL(-) (8.1%) and 22 cases were 11q23(-)/MLL(-). For some patients, different results were obtained by using CC and interphase FISH for detecting 11q23/MLL gene rearrangements. After sequential R-banding and FISH analysis for 6 patients, the chromosome related to MLL gene translocation was seen clearly in karyotypes and FISH image. It is concluded that for accurate diagnosis both CC and FISH are needed for detecting 11q23/MLL gene rearrangements, and evaluation is needed in combination of these two results. When necessary, it needs to do sequential R-banding and FISH or molecular analysis.

Study on the relationship between postmortem interval and the change of absorbance in vitreous humor of rabbit after death / 法医学杂志

OBJECTIVE@#To seek a exact method of estimating Postmortem interval (PMI).@*METHODS@#This study was preformed to investigate the relationship between postmortem interval and absorbance in vitreous humor of rabbit after death. The absorbance in vitreous humor of 48 rabbits after death were investigated with Model 754 spectrophotometer in apt wavelength (420 nm).@*RESULTS@#There exists positive linear regression association between postmortem interval (Y) and absorbance in vitreous humor (X) (r = 0.98327, P < 0.05), during rabbits after death 0 to 72 hours. The formula of linear regression is Y = 453.30 X + 0.75 (Y = postmortem interval = PMI, X = absorbance in vitreous humor).@*CONCLUSION@#The absorbance in vitreous humor can be as reference indicator to estimate PMI within hour 72.