CD5 positive B‐ALL,a uniquely aggressive subcategory of B‐ALL? A case report and brief review of the literature

CD5 antigen expression in B‐cell acute lymphoblastic leukemia (B‐ALL) is exceptionally rare. There are six detailed case reports in the literature, with only 16 cases described. Case series analyzing the frequency of aberrant B‐ALL immunophenotypes suggest that this variant may occur in as little as 2‐4.5% of all B‐ALL cases, with one series having no CD5⁺ positive cases. Herein we report a case of CD5⁺ B‐ALL in a 15‐year‐old female, and review the previously reported cases. As limited information is available, more data from prospective clinical trials are required to determine whether CD5 positivity portends a poorer prognosis.     

Morphofunctional status and osteogenic differentiation potential of human mesenchymal stromal precursor cells during <Emphasis Type="Italic">in vitro</Emphasis> modeling of microgravity effects

We studied the effects of long-term (20-day) simulated microgravity (clinostatic exposure) and osteogenic differentiation stimuli on cultured mesenchymal stromal precursor cells isolated from human bone marrow. Clinostatic exposure significantly reduced proliferative activity of mesenchymal stem cells in comparison with the static and dynamic control, increased the number of large flat cells in the culture, and stimulated migration activity of cells. Phenotypic studies of surface antigens (CD90, CD54, CD106, CD105, CD34, CD45, class 1 HLA) during clinostatic exposure of mesenchymal stem cell cultures showed differences in their expression between experimental and control groups. Studies of osteogenesis of precursor cell showed that cell differentiation potential can be directed towards osteogenesis by a combination of clinostatic exposure and differentiation stimuli. The results confirm gravity sensitivity of human bone marrow precursor cells and open new vistas for understanding of the mechanisms of bone tissue loss in humans under conditions of space mission.     

Immunophenotypic discrepancies between granulocytic and erythroid lineages in peripheral blood of patients with paroxysmal nocturnal haemoglobinuria

Abstract: In paroxysmal nocturnal haemoglobinuria (PNH), somatic mutation of the PIG‐A gene is thought to result in altered expression of glycosylphosphatidylinositol (GPI)‐anchored proteins. This study was performed to determine if there were any heterogeneities of cellular phenotypes between two major peripheral blood cells, erythrocytes and granulocytes. Using CD59‐based immunocytometry, the patterns of CD59 expression were shown to be conserved in the circulating erythroid cells (reticulocytes and mature erythrocytes) in all 29 patients with PNH. Twenty‐one patients had distinct combinations of PNH type I, II, and III cells in different lineages. Only eight patients exhibited similar patterns of CD59 expression between the two lineages. Approximately one third of the patients had PNH type II cells in either or both of the two lineages indicating variable lineage involvement. The proportion of abnormal granulocutes was higher than those of abnormal reticulocytes and erythrocytes. In patients with appropriate erythropoietic responses to haemolysis (RPI>2.0), shift reticulocytes display predominantly PNH phenotypes. These immature erythroid cells with altered expression of GPI‐anchored proteins may dominate the peripheral blood during periods of increased marrow activity resulting in greater phenotypic mosaicism in such patients. Discrepancies in expression of GPI‐anchored proteins in PNH which are highly variable between the two lineages may be the result of their different life spans and the influence of complement‐mediated cytolysis. The phenomena also indicated the possible occurrence of more than one PNH clones with variable clonal dominance.     

Clinical relevance of immunological dissection in T-ALL: a report on 20 cases with stem cell (CD7+, CD4-, CD8-, CD1-) phenotype.

In a prospective study on 44 cases of T-cell origin acute lymphoblastic leukemia, 20 patients were found to display an immature immunophenotype (CD7+, CD4-, CD8-, CD1-) and were classified as T-stem cell leukemia (T-SCL). Twenty-four patients expressed CD4 and/or CD8 antigens on their blast cells, designated T acute lymphoblastic leukemia (T-ALL). The T-SCL subset showed a significantly higher median age, a more frequent incidence of extramedullary leukemia, a morphology L1 in most cases, and a poor response to treatment in terms of either complete remission rate or median survival duration. In addition, significant differences between the two groups were found in evaluating the number of days of blast disappearance from peripheral blood, of CR achievement, and of neutrophils and platelets recovery. We conclude that T-SCL represents a distinct clinical entity, characterized by a poor response to ALL conventional chemotherapy. Alternative therapeutic approaches should be developed for patients suffering from this form of leukemia, to modify its severe prognosis.     

Monoclonal antibody fluorescence for routine lymphocyte subpopulation analysis with the Abbott CELL-DYN Sapphire haematology analyser

Using previously described procedures, this study quantified T-cell, T-cell subset, B-cell and NK-cell populations with the CD-Sapphire haematology analyser in a series of patients with mild to moderate lymphocytosis. Lymphocyte counts ranged from 6.0 to 14.9 x 10(9)/l, with 86/97 being <10.0 x 10(9)/l. Immunophenotyping (CD3/CD19/HLA-DR, CD4/CD8 and CD16/CD56 combinations) was performed using EDTA-anticoagulated blood, automated CD-Sapphire analysis and subsequent software processing. Of 35 samples from younger (<12 years) patients, 22 (63%) had nonspecific lymphocyte changes, 4 (11%) showed specific increases in nonreactive T-Helper or T-Suppressor cells, and five showed a reactive T-cell lymphocytosis. The remaining four were classified as 'Transient/Persistent NK-associated (NKa) Expansion' (n = 3) and specific B-cell lymphocytosis (n = 1). For older patients (n = 59), 15 (25%) had an increase (>1.5 x 10(9)/l) in B-cells, and seven investigated for surface immunoglobulin expression were all found to be clonal. The remaining samples were categorized as 'Transient/Persistent NK-associated (NKa) Expansion' (13/59), Reactive Lymphocytosis (5/59), 'Reactive Lymphocytosis or Transient/Persistent NKa Expansion' (8/59), specific T-Helper cell (n = 8) or T-Suppressor cell (n = 3) lymphocytosis, and 'Lymphocytosis of Undetermined Significance' (n = 7). This study has demonstrated the feasibility of applying limited immunophenotyping protocols to the investigation of patients with abnormal lymphocyte counts in routine haematology. By using commercially purchased liquid monoclonal reagents to determine lymphocyte subpopulation profiles, haematology laboratories can provide more definitive information of potential clinical importance.     

Evolution of Ig- and T-cell receptor gene configuration in a Ph1+ hybrid leukemia patient.

In a longitudinal study of a 32-year-old male with Ph1+ hybrid leukemia we have followed the immunophenotype and configuration of Ig- and TCR genes during the course of different chemotherapy regimens directed first against the myeloid and later against the lymphoid components of the disease. We identified changes in all parameters, interpretable as an evolution of the malignant clone resulting in a leukemic switch towards a more lymphoid character. Thus, while the expression of the myeloid antigens CD13 and CD33 decreased, that of CD10 (CALLA) and CD20 (B1) increased. Moreover, while the configuration of the Ig heavy and light chain lambda genes remained constant during the whole period of treatment, that of the Ig light chain kappa gene and TCR beta gene displayed extensive rearrangements after initiation of ALL therapy. Since this patient represents a de novo acute leukemia as evaluated by location of the translocation-breakpoint on chromosome 22, our data clearly indicate that Ig- and TCR gene rearrangements might prove a valuable addition in monitoring Ph1+ hybrid leukemias, providing guidelines for optimizing chemotherapy.     

Immunophenotypic shift of memory CD8 T cells identifies the changes of immune status in the patients after liver transplantation

Abstract

Objective: Chronic or acute rejection is a leading cause of allograft loss after solid organ transplantation and the presence of memory T cells is associated with increased propensity for allograft rejection. The purpose of this study was to investigate the correlation between immunophenotypic shift of memory CD8⁺ T cells and immune status in the patients after liver transplantation. Material and methods: Seventy-three blood samples were collected and varied compartments of memory CD8⁺ T cells were analysed in non-rejected and rejected patients. Results: The results show that with time elapsed, the immunophenotypes of memory CD8⁺ cells shifted from naive T cells to central or intermediate memory cells, and then to effector or terminal memory cells in non-rejected patients. This course was correlated with the expression of CD127 on CD8⁺ T cells. In rejected patients, the main proportion of CD8⁺ cells were dominated by naive CD8⁺ cells and then rapidly restored to the immunophenotypes of memory T cells after effective treatment. Conclusion: These results demonstrated that immunophenotypic shift of memory CD8⁺ T cells was closely related to the change of the immune status in the patients after liver transplantation. Monitoring the immunophenotypic shift of memory CD8⁺ T cells is of great importance in the prediction for allograft rejection and treatment effectiveness after liver transplantation.     

多参数流式细胞术分析505例急性淋巴细胞白血病跨系列表达方式

跨系列抗原表达是白血病免疫表型的一个重要特征。对于急性淋巴细胞白血病（ALL）的跨系表达方式,目前国内尚缺乏大样本多参数的研究报道。本研究利用三色流式细胞术探讨505例ALL（431例B—ALL,74例T—ALL）患者23种系相关抗原的跨系表达方式。结果显示：全部ALL病例中,髓系抗原的表达率为56．4％,其中以CD13（32．7％）的表达最常见,其次为CD33（29．5％）、CD15（19．2％）和CD11b（7．7％）。CD13／CD33在CD34^＋病例中的表达高于CD34^＋病例。在B—ALL中,T系抗原CD4、CD5、CD7和CD2的表达率依次为6．3％、2．8％、1．9％和1．4％,并且CD7^＋、CD2^＋和CD4^＋病例通常共表达CDl3和（或）CD33。在T—ALL,B系抗原cCD79a、CD19和CD22的表达率分别为8．1％、6．8％、和2．8％,而全部CD19和CD22表达者均伴CD13／CD33表达。结论：ALL的跨系袁达多存在未成熟的阶段,以跨髓系抗原的表达最常见（B^＋M^＋,T^＋M^＋）,偶有B系、T系和髓系抗原的共表达（B^＋T^＋M^＋）,仅有B系和T系跨系表达的极少（B^＋T^＋M^-）。     

试论当前医学院校人文学科建设的若干对策

论述了医学院加强人文学科建设的必要性，并分析了目前医学院校人文学科的现状和课程体系的设置，提出加强人文学科建设的对策。