Phenotypic similarities and differences between CALLA-positive acute lymphoblastic leukemia cells and normal marrow CALLA-positive B cell precursors

Expression of differentiation markers in common acute lymphoblastic leukemia (cALL) cells from 25 patients was compared with subpopulations of normal common ALL antigen (CALLA) (CD10)-positive bone marrow lymphoid cells (cBMLs). In cBML, CD10 intensity is positively correlated with CD34 (MY10) and terminal transferase (TdT) expression and inversely correlated with common leukocyte antigen (CLA), CD20 (B1), and ctyoplasmic mu chain (Cmu) expression. In cALL, CD10 density was inversely correlated with CLA and Cmu expression and strongly correlated with CD34 expression as in cBML. In contrast to cBML, TdT and CD20 expression were not related to CD10 density in cALL. Furthermore, cALL TdT intensity measured by enzyme immunoassay was not related to expression of CD10, CLA, or CD34, but was positively correlated with CD20 expression. Cmu expression in cALL was inversely correlated with expression of CD34 and positively correlated with CLA as in cBML, but showed no association with TdT intensity or CD20 expression in contrast to the relationship found in cBMLs. Analysis of TdT intensity and Cmu expression in sorted subpopulations of cells from individual patients that were positive or negative for CD34, CD20, or CD10 was consistent with the data obtained by comparison of cells from different patients. These results indicate that from patient to patient and within individual patients, cALL cells express the markers CD34, CLA, CD10, and Cmu in a coordinated fashion similar to cBMLs, but demonstrate differences in expression of TdT and CD20 with respect to the marrow cells considered their normal counterparts. The cALL cells that are CD34 positive show increased expression of CD10 and are less likely to be CLA or Cmu positive, suggesting that they may represent a phenotypically less differentiated form of cALL than does CD34-negative cALL.     

Hematologic effects of immunotherapy with lymphokine-activated killer cells and recombinant interleukin-2 in cancer patients

Immunotherapy with interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells generated from autologous lymphocytes has produced significant tumor regressions in patients with advanced cancer. In the current study, we reviewed the hematologic effects associated with this therapy in our initial 42 patients. Eighty-eight percent of the treated patients developed anemia that required greater than or equal to 4 units of red cell transfusions, and 43% received at least 8 units. Only a blood loss of 2 to 3 units could be attributed to repeated phlebotomy, cytophereses, and hemodilution. IL-2 administration also resulted in thrombocytopenia as well as lymphopenia and eosinophilia. Forty-three percent of patients developed platelet counts of less than or equal to 50,000/microL, and 36% of the total group required platelet transfusions. Mild neutropenia and a rebound lymphocytosis followed discontinuation of IL-2 treatment. To explore the possible mechanisms for these hematologic effects, standard hematopoietic colony assays were conducted on serial blood samples from five patients. IL-2 produced a significant decline in circulating erythroid (BFU-E) and granulocytic/macrophage (CFU-C) progenitors, which rebounded after the discontinuation of IL-2 therapy. Infusion of IL-2 also resulted in measurable serum levels of gamma-interferon. Some of the hematologic effects of immunotherapy with LAK cells and IL-2 may be the result of IL-2-mediated suppression of hematopoiesis.     

肠道微生物群对炎症性肠病的影响

古语说,为了解整体首先必须了解其组成部分.这同样适用于对人的胃肠道研究.正如生物学中大多数领域,我们已经积累了关于该系统分化和特异性的大量知识.从大体解剖到分子生物学,我们在组织、细胞和亚细胞水平对于肠道的功能和工作过程有了较为详细的了解.虽然已将现有的遗传调节和生物化学技术应用于人类研究,至今仍然只见树木不见森林.在以宿主为中心的工作重点中,仍然未能充分认识最小组成部分的作用,即我们常驻的微生物.