Biomedical subjects

Yangqiu Li

Publications and source records attributed to Yangqiu Li.

12 recordsLinked to original sources

PubMed2005

Clonal expanded TCR Vbeta T cells in patients with APL.

T-cell receptor Vss gene repertoire and clonality have been studied in patients with leukemia and solid tumors, by assaying the CDR3 size of TCR genes, using RT-PCR and genescan analysis. Few studies have studied leukemia-associated oligoclonal expanded T-cells in leukemia, therefore, the aim of this study was to investigate the distribution and clonal expansion of T-cell receptor, Vss subfamily T-cells in patients with acute promyelocytic leukemia (APL) with t(15;17). The CDR3 of TCR Vbeta24 subfamily genes were analyzed in peripheral blood mononuclear cells from 17 cases with PML-RARalpha+ APL using RT-PCR and genescan technique. Ten normal individuals served as controls. The results showed that the number of expressed Vss subfamilies (from 2 to 21 subfamilies) varied in different patients with APL. The most frequently expressed Vss subfamilies were Vbeta2 (64.7%), Vbeta15 (58.8%), Vbeta3 and Vbeta5 (47.1%), with a lower expression rate found in Vbeta11 and Vbeta20 (11.7%). Clonally expanded T-cells in the Vss subfamilies could be identified in patients with APL in all but two of the cases studied, predominantly in Vbeta10, Vbeta23, Vbeta3 and Vbeta21. In conclusion, skewed distribution and clonal expansion of TCR Vss subfamily T-cells could be found in patients with APL. The clonal expansion of T-cells were considered to be a specific anti-leukemic immune response by host T-cells activated by the leukemia-associated-antigen.

Adolescent↗

PubMed2005

KDR and Sema3 genes expression in bone marrow stromal cells and hematopoietic cells from leukemia patients and normal individuals.

Kinase domain receptor (KDR) and Semaphorin3 (Sema3) have a functional relationship and are expressed in human bone marrow (BM). We cultured in vitro bone marrow stromal cells (BMSCs) and collected nonadherent cells from patients with acute myeloid leukemia (AML), chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL) and normal individuals. Reverse transcriptase polymerase chain reaction enzyme-linked immunosorbent assay (RT-PCR-ELISA) was performed to examine KDR and Sema3 genes expression, using beta2 microglobulin as an internal reference. KDR expression ratio in normal control BMSCs (97.0%, 32/33) was higher than in its corresponding nonadherent cells (70.8%, 17/24). KDR expression levels in ALL BMSCs and AML nonadherent cells were significantly higher than in normal controls. Sema3 expression ratios in nonadherent cells from AML (78.6%, 11/14) and CML (71.4%, 10/14) were both significantly lower than in normal control (100%, 27/27), its expression levels were also significantly lower than in normal control. Sema3 expression level in normal BMSCs was significantly lower than in nonadherent cells. Sema3 and KDR genes expression levels displayed a significantly positive correlation in normal control and ALL nonadherent cells (r=0.703, P=0.002; r=0.999, P=0.001). These results suggests that KDR may play a critical role in sustaining the hematopoietic microenvironment due to its high expression, and that KDR may be involved in pathogenesis of AML and ALL. Sema3 could also sustain the survival of hematopoietic cells with its high expression, while Sema3 gene expression may be inhibited in AML and CML.

Adolescent↗

PubMed2005

Recent thymic output function in patients with hematological malignancy.

Thymic function is important for the generation of T-cell diversity in the periphery of both children and adults during both health and disease. Until recently, thymic function could not be monitored, as a consequence of the absence of adequate technology to differentiate recent thymic emigrants (RTEs) from naïve T cells. The generation of TCR diversity occurs in the thymus through recombination of gene segments encoding the variable parts of the TCR alpha and beta chains. During these processes, by-products of the rearrangements are generated in the form of signal joint T-cell receptor excision circles (sjTRECs). As sjTRECs are stable extrachromosomal DNA fragments, they are not replicated during mitosis and thus diluted with each round of cell division, and are therefore most frequent in naïve T cells that have recently left the thymus, their quantification is actually considered as a valuable tool to estimate thymic function. Therefore, quantitative sjTRECs content have been recently used to assess thymic output during both health and disease. In this review, we summarize recent data on the recent thymic output function feature in patients with hematological malignancy and the immune reconstitution after stem cell transplantation and we also characterize factors that may improve the thymic output function.

DNA Replication↗

PubMed2005

The TCR Vbeta repertoire usage of T-cells from cord blood induced by chronic myelogenous leukemia associated antigen.

Understanding the clonality and restricted usage of the TCR Vbeta repertoire of expanded T-cells induced by the chronic myelogenous leukemia (CML) associated antigen may be useful in helping design new immunotherapeutic strategies specifically for CML. T-cells from cord blood that had been stimulated by different stimulators (IL-2, PHA, CML cells, K562 cells and bcr-abl peptide) were amplified in vitro by liquid T-cell culture and the mixed lymphocyte and tumor cell culture (MLTC) method. By using the RT-PCR, the CDR3 segments of 24 variable region genes of TCR beta was analyzed in T-cells from 22 cases of cord blood before and after T-cell culture, to observe the usage of TCR Vbeta repertoire. The PCR products were further labeled with fluorescence and analyzed by the Genescan technique for the CDR3 size, to evaluating clonality of the detectable TCR Vbeta T-cells. Only a part of 24 Vbeta subfamily T-cells (3-15 subfamilies) could be detected, however, all of the 24 TCR Vbeta subfamily of T-cells were detected after in vitro culture with PHA or IL-2+anti-CD3 antibody. The number of expressed TCR Vbeta subfamilies was gradually reduced by prolonging the time of culture with CML-associated antigens. The restricted expression of TCR Vbeta subfamilies and oligoclonal expansion of Vbeta21 T-cells were found in cultured T-cells induced by CML cells, K562 cells or bcr-abl peptide. In conclusion, T-cells from cord blood may have the potential capability of proliferation in different TCR Vbeta subfamily T-cells, and the ability for restricted expression and clonal expansion, when T-cells were induced by CML associated antigen.

Cell Proliferation↗

PubMed2003

Leukemia associated clonal expansion of TCR Vbeta subfamily T cells.

The analysis of the T cell receptor (TCR) Vbeta repertoire is one of the most sensitive methods to identify the clonal expansion T cells which respond to tumor associated antigens. Recently, studies have focused on clonally expanded T cells from patients or normal donors induced by leukemia associated antigens in vivo or in vitro. Understanding such clonality and restricted usage of TCR Vbeta repertoire of leukemia-associated expanded T cells may be useful for the design of new immuno-therapeutic strategy for leukemia.

Humans↗

PubMed2002

Clonal expansion T cells identified in acute monoblastic leukemia by CDR3 size analysis of TCR V beta repertoire using RT-PCR and genescan.

OBJECTIVE: To investigate the distribution and clonality of T cell receptor (TCR) V beta repertoire in patients with acute monoblastic leukemia (AML-M5). METHODS: Expression of the TCR V beta repertoire was analyzed using reverse transcription-polymerase chain reaction (RT-PCR), which amplified the complementarity determining region 3 of 24 TCR V beta genes in peripheral blood from 9 cases with acute myclogenous leukemia subtype 5 or acute monoblastic leukemia (AML-M5). PCR products were further studied by genescan analysis to identify T cell clonality. RESULTS: Expression of 1-10 V beta subfamilies was found in samples from 9 patients. Genescan analysis showed that some V beta subfamily products from 8 of 9 cases contained an oligoclonal peak. Oligoclonal T cells of the V beta 2 subfamily could be found in 6 patients with AML-M5. CONCLUSIONS: T cell clonality expansion was found in AML-M5 cases and were tendentious in the V beta 2 subfamily, suggesting a the specific immune response for leukemia cell (M5) associated antigen and may display antileukemia activity.

Complementarity Determining Regions↗

PubMed2000

[The Insertional Mutation of Transcription Factor GATA-2 Gene in Acute Non-Lymphocytic Leukemia]

To investigate the expression and mutation of transcription factor GATA-2 gene in acute non-lymphocytic leukemia (ANLL), the GATA-2 gene were amplified in peripheral blood mononuclear cells from 85 cases with ANLL using RT-PCR, and the PCR products were further analyzed by single strand conformation polymorphism (SSCP) and sequencing. The results showed that GATA-2 gene was expressed in the most cases with ANLL (89.4%). One larger band was observed by RT-PCR in a case with M(1) subtype. Nucleotide sequence analysis revealed a insertion of 18 nucleotides at position 1 288 bp of the GATA-2 gene cDNA, thereby leading to 6 additional amino acids in second zinc finger complex of GATA-2, and it includes a cysteine which can bind to zinc ion. The insertional mutation may change the function of GATA-2 transcription factor. To our knowledge this is the first description of insertional mutation in the GATA-2 gene.

Journal Article↗

PubMed2000

[Detection of Human Herpesvirus-6 DNA in Peripheral Blood Cells of Patients with Myelogenous Leukemia by Nested PCR]

Human herpesvirus-6 (HHV-6) is largly disseminated in human population, which may relate to many diseases. Due to different methods previously used, the results of HHV-6 DNA detections in patients with leukemia are not identical. With a control-study, HHV-6 DNA in the blood cells from 38 cases, including 30 cases with acute myeloid leukemia and 8 cases with chronic myelogenous leukemia was detected by nested PCR. The results showed that HHV-6 DNA positive rate (63%) in patients with AML was lower than that in controls, whereas no significant difference between patients with CML (75%) and controls (92%) was shown. The clinical importance of HHV-6 infections in myelogenous leukemia should continue to be investigated later.

Journal Article↗

PubMed2000

[Expression of the Cholinesterase-Related Cell Division Controller Gene in Peripheral Blood Cell from Patients with Myelodysplastic Syndrome]

To investigate the expression of the cholinesterase-related cell division controller (CHED) gene in the patients with myelodysplastic syndrome (MDS), CHED gene expression was assayed by RT-PCR and its relative expression rate (RER) was determined by the semi-quantitative RT-PCR analysis in peripheral blood mononuclear cells from 21 patients with MDS, 12 normal individuals served as controls. Results showed that RER of CHED in the patients (2.69 +/- 0.76) was significantly higher than that in controls (1.12 +/- 0.51, P < 0.01), the RER out of 85.7% of the patients was higher than the mean value of the controls, in which three patients developed into acute leukemia; the RER out of 61.9% of the patients was higher than the upper limit of the mean value of the controls; three patients whose RER was lower than the mean value of the controls did not developed into leukemia. These findings suggested that the expression of CHED gene in patients with MDS was significantly higher than in controls.

Journal Article↗

PubMed2000

[The Feature of Skewing Distribution of TCR Vbeta T Cells from Peripheral Blood and Bone Marrow in Patients with AML-M(5)]

The TCR Vbeta 24 subfamily genes were amplified in peripheral blood and bone marrow mononuclear cells from 5 cases with acute monocytic leukemia (AML-M(5)) using RT-PCR, to observe the distribution of TCR Vbeta subfamilies. The results indicated that 1 - 19 Vbeta subfamily T cells could be identified in different samples from AML-M(5) cases. The variation of distribution of TCR Vbeta subfamily T cells could be found in different individual samples. The results provided the feature of cell immune function change in skewed distribution of TCR Vbeta subfamily T cells from peripheral blood and bone marrow of patients with AML-M(5).

Journal Article↗

PubMed2000

[Advance of Research on Treatment of Donor Lymphocyte Infusions in Relapse of Hematologic Malignancies after Allogeneic Bone Marrow Transplantation]

The applications of allogeneic bone marrow transplantation (allo-BMT) are limited by the high risk of relapse with primary malignancy. The newly adaptive immunotherapy with donor lymphocyte infusions (DLI) can induce an effective graft-versus-leukemia (GVL) reaction leading to molecular remission and prolonged disease free survival in the majority of patients with relapse of CML and some other hematologic malignancies. Little is known about the mechanisms and the kinetics of GVL, however, increasing evidences show that in the case of existence of chimerism the mature donor T lymphocytes are activated by the specific leukocyte artigen presented in the surface of host antigen presenting cells (APC), resulting in exclusively elimination of leukocyte. Undesired side-effects are the development of graft-versus-host disease (GVHD) and the occurrence of pancytopenia in some patients. Infusions with selective T lymphocytes and G-CSF-mobilized peripheral blood stem cells (PBSC) are the promising treatment of DLI for more patients.

Journal Article↗

PubMed2000

The Role of Transcription Factor GATA-2 in Early Hematopoiesis.

Transcription factor GATA-2 is a member of GATA family which binds a common DNA sequence motif [T/A (GATA) A/G] through an evolutionarily conserved zinc finger domain. An essential role for GATA-2 in the development of hematopoietic cells has recently been shown in gene knockout experiments in mice. GATA-2 gene disruption makes reduction in all hematopoietic precursors, whereas enforced expression of GATA-2 blocks normal hematopoiesis. GATA-2 exerts regulation in early embryo and cooperates with other GATA transcription factors in proliferation and differentiation of myeloid, erythroid, megakaryocytic and mast cell lineages. GATA-2 mRNA and protein could be detected in human myelogenous leukemia cell lines and in most patients with primary leukemias. Some data revealed that GATA-2 could transactivate the Cas-Br-E and graffi retroviruses, which can induce myelogenous leukemia in mice. However, the role of GATA-2 in pathogenesis of leukemia is still not well understood.

Journal Article↗