Abstract:
UNLABELLED:In this paper we describe an experimental model for ex vivo purging of contaminating tumor cells from peripheral blood stem cell (PBSC) collections obtained from patients with acute myeloblastic leukemia (AML). We studied the combination of the alkylating agent nitrogen mustard (NM; concentrations ranging from 0.25 to 1.25 microg/mL) and etoposide (VP-16; constant dose of 20 microg/mL), and the conventional cyclophosphamide (Cy)-derivative mafosfamide (concentrations: 20-175 microg/mL). THE AIMS OF OUR STUDY WERE:1) To compare the toxicity of the purging protocols on bone marrow (BM) and circulating trilineage precursors collected from normal donors after priming with granulocyte colony-stimulating factor (G-CSF) or after complete remission (CR) consolidation chemotherapy and G-CSF (leukemic patients); 2) to demonstrate the survival of very primitive hematopoietic progenitors (LTC-IC) in the peripheral blood (PB) and the BM after pharmacological treatment; and 3) to evaluate the antineoplastic efficacy of purging protocols on PBSC collections using 3 well-established leukemic cell lines. Our results demonstrated that the toxicity on BM and PB progenitor cells could be correlated with the complete killing of committed granulocyte-macrophage colony-forming units (CFU-GMs) and erythroid precursors (BFU-Es), a condition reached at the concentration of 1.5 microg/mL of NM (in addition to 20 microg/mL of VP-16) and 175 microg/mL of mafosfamide. Notably, early and late megakaryocyte progenitor cells (CFU-MKs and BFU-MKs, respectively) showed higher sensitivity to NM/VP-16, but not to mafosfamide, than did CFU-GMs and BFU-Es. The dose of NM capable of inhibiting 95% of CFU-MKs and BFU-MKs (ID95) was 0.75 microg/mL. After incubation with the same dose of NM, the recovery of CFU-GMs and BFU-Es was 20 +/- 8% SD and 25 +/- 10% SD, respectively (p < 0.05). Long-term liquid cultures showed the recovery of primitive hematopoietic cells after incubation with the highest concentrations of NM/VP-16 and mafosfamide, with no significant differences between PB and BM samples. Under the same experimental conditions, we observed a more than 5-log reduction of contaminating leukemic cell lines (i.e., K-562, KG-1, and HL-60). In conclusion, we demonstrated that NM/VP-16 and mafosfamide purging agents are capable of killing leukemic cell lines that contaminate leukapheresis products from patients with AML, whereas an acceptable proportion of primitive LTC-IC is spared. Moreover, despite the different kinetic and functional profile of mobilized and steady-state BM progenitors, we did not observe any difference in toxicity of antineoplastic agents on hematopoietic cells at different levels of differentiation. These data suggest that pharmacological strategies developed for eliminating minimal residual disease (MRD) from BM autografts can be effectively and safely applied to circulating stem cell harvests.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Motta MR,Mangianti S,Rizzi S,Ratta M,Campanini E,Fortuna A,Fogli M,Tura S,Lemoli RMsubject
Has Abstractpub_date
1997-11-01 00:00:00pages
1261-9issue
12eissn
0301-472Xissn
1873-2399journal_volume
25pub_type
杂志文章abstract::The human cell line CMK spontaneously expresses megakaryocytic characteristics and can be induced to differentiate into mature megakaryocytes after exposure to 12-O-tetradecanoylphorbol-13-acetate (TPA). In comparison with CMK, we have examined the characteristics of a subclone, designated as CMK11-5, that is morpholo...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1991-10-01 00:00:00
abstract::Activation of the N-ras gene via coding region mutations has been previously documented in 25% of patients with acute myeloid leukemia (AML). Since overexpression of normal N-ras is also transforming in vitro, the N-ras promoter of AML patients was analyzed for the presence of promoter mutations that may affect expres...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1995-09-01 00:00:00
abstract:OBJECTIVE:Several transducing molecules, including JAK2, STAT5, MAP kinases, phosphatidylinositol 3-kinase (PI3K), phospholipase C-gamma1, and PKC are activated by interaction between erythropoietin (EPO) and the EPO receptor. The aim of this was to examine the relative involvement of PI3K in the development of glycoph...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(02)00868-8
更新日期:2002-09-01 00:00:00
abstract::In the accompanying paper we constructed a model for the proliferation and differentiation of granulocyte-macrophage progenitor cells in response to the specific proliferation/differentiation stimulus granulocyte-macrophage colony-stimulating activity (gm-CSA). Here we have tested the model without altering the model ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-02-01 00:00:00
abstract::The cloning efficiency of T-lymphocyte progenitor cells (CFU-T) is dependent on mononuclear cell concentration, with a triphasic growth curve. At low plating cell concentrations, hydrocortisone causes a dose-dependent decrease in cloning efficiency, whereas at high cell concentrations hydrocortisone causes increased c...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-02-01 00:00:00
abstract::Megakaryocytes have been implicated in the micro-environmental abnormalities associated with fibrosis and hematopoietic failure in the bone marrow (BM) of primary myelofibrosis (PMF) patients, the Philadelphia-negative myeloproliferative neoplasm (MPN) associated with the poorest prognosis. To identify possible therap...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章
doi:10.1016/j.exphem.2019.10.001
更新日期:2019-11-01 00:00:00
abstract::Lithium (Li) is a known stimulator of steady-state granulopoiesis, influencing both pluripotential (CFUS) and granulocyte-macrophage committed stem cell (CFUGM) populations. Li has therefore been suggested to be an effective agent to reduce the neutropenia that often is seen after either cytotoxic chemotherapy or radi...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1983-07-01 00:00:00
abstract::Marrow from Sl/Sld mice (in which the hemopoietic stromal microenvironment is defective), when implanted beneath the renal capsule of a normal littermate, produces an ectopic marrow site containing the same number of stem cells (CFU-S) and nearly as many GM-CFC as that obtained by implanting marrow from a normal litte...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-03-01 00:00:00
abstract::The retroviral vector N2, which is derived from the Moloney murine leukemia retrovirus, was used to transfer the bacterial NeoR gene (conferring resistance to the neomycin analogue G418) into hematopoietic progenitor cells from fetal, neonatal, and adult dogs and cats. Infection of canine and feline bone marrow cells ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1990-03-01 00:00:00
abstract:OBJECTIVE:Endothelial progenitor cells (EPCs) are used for angiogenic therapies or as biomarkers to assess cardiovascular disease risk. However, there is no uniform definition of an EPC, which confounds EPC studies. EPCs are widely described as cells that coexpress the cell-surface antigens CD34, AC133, and vascular en...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.04.002
更新日期:2007-07-01 00:00:00
abstract:OBJECTIVE:A marker for hematopoietic stem cells (HSCs) of pigs, which are considered to be the most suitable donors for clinical xenotransplantation, has not yet been identified. In this study, we examined the HSC activity of porcine c-kit+ bone marrow cells (BMCs). METHODS:The HSC activity of porcine c-kit+ BMCs was ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(03)00197-8
更新日期:2003-09-01 00:00:00
abstract::Normal human peripheral blood mononuclear cells (MNCs), particularly T lymphocytes (T cells), are a rich source of granulocyte-macrophage colony-stimulating factor (GM-CSF). Glucocorticoids are known to inhibit GM-CSF production in in vitro cultures of a human fibroblast cell line and in normal human blood monocytes a...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1998-12-01 00:00:00
abstract::Recently we have described a CD4+ human T-cell hybridoma Ft.F3 (ATCC HB 9713). This hybridoma produces two proteins having molecular weights of 29 kd (P29) and 14.7 kd (P14.7) that function as activators of human monocyte tumor cytotoxicity and interleukin 1 (IL-1) synthesis (macrophage cytotoxicity-inducing factors, ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1991-08-01 00:00:00
abstract::Bone marrow-derived mast cell precursors form large mast cell colonies in methylcellulose and are designated as L-CFU-Mast. The effect of differentiated mast cells on recruitment and differentiation of L-CFU-Mast was investigated by using genetically mast cell-deficient WBB6F1-W/Wv mice. Giant granules of C57BL/6-bgJ/...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1990-03-01 00:00:00
abstract::The modulatory effect of 1,25 dihydroxyvitamin D3 (vit D) and 13 cis retinoic acid (retinoic acid) on the growth and differentiation of normal human pluripotent stem cell, erythroid, and myeloid progenitor cell growth was studied using semisolid methylcellulose clonal assay. Dose response curves showed that maximal in...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1986-01-01 00:00:00
abstract::Mouse megakaryocyte colonies developed in a fibrin clot culture system were morphologically classified into three types: immature homogeneous (IH), heterogeneous (H), and mature homogeneous (MH) colonies. The colony size (number of megakaryocytes per colony), the ploidy distribution of megakaryocytes in colonies, and ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1990-06-01 00:00:00
abstract:OBJECTIVE:Our previous studies have demonstrated differentially expressed genetic signature patterns in adult peripheral blood (APB) monocytes (Mos) vs cord blood (CB) Mos. MATERIALS AND METHODS:In this study, we examined the differential gene expression profiles of APB vs CB immature dendritic cells (iDCs) and mature...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2009.07.010
更新日期:2009-10-01 00:00:00
abstract::The Fanconi anemia group C gene (FAC) encodes a 63-kDa protein that plays a role in the growth and differentiation of hematopoietic progenitor cells and in cellular resistance to bifunctional cross-linking agents. The function of the gene product is unknown, as are the factors that govern expression of the gene itself...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
abstract::After initially successful chemotherapy, relapse frequently jeopardizes the outcome of patients with acute leukemia. Because of their adverse characteristics of self-renewal and dormancy, leukemia stem cells have been hypothesized to play a critical role in resistance to antiproliferative chemotherapy and the developm...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2018.09.006
更新日期:2019-01-01 00:00:00
abstract::The mechanism of localization, migration, and regulation of hematopoiesis at different stages of ontogeny is not well understood, but may relate to the specific adhesive interactions between hematopoietic stem cells and their microenvironment at different ontogenic stages. We studied the expression of cell adhesion mo...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(98)00031-9
更新日期:1999-02-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to develop novel markers for enrichment of hematopoietic progenitors from bone marrow of swine. MATERIALS AND METHODS:We previously showed that pig bone marrow contains a "side population" (SP) of Hoechst dye-effluxing cells that resembles the hematopoietic stem cell (HSC)-containin...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(02)00835-4
更新日期:2002-07-01 00:00:00
abstract::Benign constitutional neutropenia (BCN) is an asymptomatic condition characterized by mild chronic neutropenia in patients with no history of recurrent infections. Most patients are referred for further testing, increasing health care costs. We present an alternative form of assessment of individuals with BCN based on...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章
doi:10.1016/j.exphem.2018.10.007
更新日期:2019-01-01 00:00:00
abstract:OBJECTIVE:The retinoic acid receptors (RARs) alpha, beta2, and gamma regulate specific subsets of target genes during all-trans retinoic acid (RA) induced differentiation of F9 teratocarcinoma stem cells. The Tie1 gene exhibited reduced expression in RA-treated F9 RARgamma-/- cells as compared to wild-type (WT) by micr...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.12.016
更新日期:2008-05-01 00:00:00
abstract::Fabry disease is a lysosomal storage disorder that is due to a deficiency in alpha-galactosidase A (alpha-gal A). Previously we have shown that a recombinant retrovirus synthesized for the transfer of the human alpha-gal A coding sequence was able to engineer enzymatic correction of the hydrolase deficiency in fibrobl...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(99)00050-8
更新日期:1999-07-01 00:00:00
abstract:OBJECTIVE:These studies were performed to test the hypothesis that DNMT1 is required for maintenance of DNA methylation and repression of the γ-globin gene in adult-stage erythroid cells. MATERIALS AND METHODS:DNMT1 levels were reduced by nucleofection of small interfering RNA targeting DNMT1 in chemical inducer of di...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2010.10.003
更新日期:2011-01-01 00:00:00
abstract::Cell proliferation was investigated in normal and Rauscher Leukemia Virus-infected BALB/c mice. Five days after inoculation, islands of leukemic blasts arose in the red pulp, and proliferated as shown by autoradiographic analysis after a pulse of 3H-Thymidine. These cells subsequently infiltrated the whole spleen and ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1978-06-01 00:00:00
abstract::Mice of the RF strain are unusually susceptible to the development of leukemia, both spontaneously and after whole body irradiation. Cell culture and transplantation techniques were used to study the proliferative capacity of hematopoietic tissues of these mice. The growth characteristics of granulopoietic cells of yo...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1980-09-01 00:00:00
abstract::An 18-year-old male with severe aplastic anemia associated with hepatitis was prepared for bone marrow transplantation with cyclophosphamide (50 mg/kg/day) for 4 consecutive days. He then received 3.47 X 10(8) nucleated bone marrow cells per kilogram of body weight from his HL-A identical sister by intravenous infusio...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1977-01-01 00:00:00
abstract:OBJECTIVE:Hematopoietic progenitor cells are a promising source for generation of genetically modified dendritic cells. A prerequisite for using these cells in therapeutic approaches is stable vector-mediated transgene expression during and after cell maturation. We investigated the expression of enhanced green fluores...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(01)00778-0
更新日期:2002-02-01 00:00:00
abstract::Marrow obtained from mice (referred to as [X + BM] mice) 3 months after gamma-irradiation (9 Gy) and bone marrow inoculation (0.1 femur equivalents) showed a reduced capacity to reconstitute hemopoiesis of irradiated mice and an increased sensitivity to 5-fluorouracil. Sorting of marrow from (X + BM) mice on the basis...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-05-01 00:00:00