Histidine Decarboxylase (HDC) as Novel Marker of Immature Neoplastic Mast Cells in Systemic Mastocytosis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4755-4755
Author(s):  
Maria T. Krauth ◽  
Hermine Agis ◽  
Karl J. Aichberger ◽  
Ingrid Simonitsch ◽  
Leonhard Muellauer ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cells ◽  
Progenitor Cells ◽  
Histidine Decarboxylase ◽  
Systemic Mastocytosis ◽  
Bone Marrow Involvement ◽  
Hematopoietic Progenitor Cells ◽  
Pcr Analysis ◽  
Maturation Stage ◽  
Hematopoietic Progenitor

Abstract Synthesis of histamine in hematopoietic progenitor cells may be one of the earliest events in mast cell-development from pluripotent hematopoietic progenitor cells. In the present study, we asked whether the key enzyme involved in histamine generation, histidine decarboxylase (HDC), can be employed as an immunohistochemical marker for the detection of (neoplastic) mast cells (MC) in patients with cutaneous (CM) or systemic mastocytosis (SM). To address this question, we examined bone marrow biopsy specimens in a cohort of 101 patients (CM, n=10; indolent SM, n=46; SM with associated clonal non-MC lineage disease, n=31; aggressive SM, n=10; MC leukemia, n=3; MC sarcoma, n=1) using an antibody against HDC. Independent of the maturation stage of MC or subtype of disease, the anti-HDC antibody produced clear diagnostic staining results in all patients with bone marrow involvement examined including those with MC leukemia and MC sarcoma, in which MC are particularly immature and often escape analysis when examined by conventional stains. In these patients (MC leukemia, n=2; MC sarcoma, n=1), expression of HDC was reconfirmed at the mRNA level by RT-PCR analysis performed with RNA of highly enriched sorted CD117+ MC. In patients with CM or normal/reactive bone marrow (n=30), no HDC-positive infiltrates were detected. In these patients, only a few hematopoietic cells, presumably basophils, were found to react with the anti-HDC antibody. In summary, HDC is expressed in neoplastic bone marrow MC in patients with SM independent of the maturation stage of cells or the variant of disease. HDC should therefore be considered as a new MC marker in the screen panel of antigens employed to diagnose high grade MC malignancies.

scholarly journals Single-cell analysis reveals the KIT D816V mutation in hematopoietic stem and progenitor cells in systemic mastocytosis: Supplementary data

2018 ◽  
Author(s):  
Jennine Grootens ◽  
Johanna S Ungerstedt ◽  
Maria Ekoff ◽  
Elin Rönnberg ◽  
Monika Klimkowska ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cells ◽  
Single Cell ◽  
Progenitor Cells ◽  
Systemic Mastocytosis ◽  
Cell Subset ◽  
Tyrosine Kinase Receptor ◽  
Hematopoietic Progenitor ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells

Background: Systemic mastocytosis (SM) is a hematological disease characterized by organ infiltration by neoplastic mast cells. Almost all SM patients have a mutation in the gene encoding the tyrosine kinase receptor KIT causing a D816V substitution and autoactivation of the receptor. Mast cells and CD34+ hematopoietic progenitors can carry the mutation, however, in which progenitor cell subset the mutation arises is unknown. We aimed to investigate the distribution of the D816V mutation in single mast cells and single hematopoietic stem and progenitor cells. Methods: Fluorescence-activated single-cell index sorting and D816V mutation assessment were applied to analyze mast cells and more than 10,000 CD34+ bone marrow progenitors across 10 hematopoietic progenitor subsets. In vitro assays verified cell-forming potential. Findings: We found that in SM 60-99% of the mast cells harbored the D816V mutation. Despite increased frequencies of mast cells in SM patients compared with control subjects, the hematopoietic progenitor subset frequencies were comparable. Nevertheless, the mutation could be detected throughout the hematopoietic landscape of SM patients, from hematopoietic stem cells to more lineage-primed progenitors. In addition, we demonstrate that FcεRI+ bone marrow progenitors exhibit mast cell-forming potential, and we describe aberrant CD45RA expression on SM mast cells for the first time. Interpretation: The KIT D816V mutation arises in early hematopoietic stem and progenitor cells and the mutation frequency is approaching 100% in mature mast cells, which express the aberrant marker CD45RA.

scholarly journals FGF2 posttranscriptionally down-regulates expression of SDF1 in bone marrow stromal cells through FGFR1 IIIc

Blood ◽  
2006 ◽  
Vol 109 (4) ◽  
pp. 1363-1372 ◽  
Author(s):  
Takayuki Nakayama ◽  
Noriko Mutsuga ◽  
Giovanna Tosato
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Stromal Cell ◽  
Marrow Stromal Cells ◽  
Hematopoietic Progenitor Cells ◽  
Pcr Analysis ◽  
Hematopoietic Progenitor ◽  
Stromal Cell Derived Factor

AbstractThe chemokine stromal cell–derived factor-1 (SDF-1) is constitutively expressed by bone marrow stromal cells and plays key roles in hematopoiesis. Fibroblast growth factor 2 (FGF2), a member of the FGF family that plays important roles in developmental morphogenic processes, is abnormally elevated in the bone marrow from patients with clonal myeloid disorders and other disorders where normal hematopoiesis is impaired. Here, we report that FGF2 reduces SDF-1 secretion and protein content in bone marrow stromal cells. By inhibiting SDF-1 production, FGF2 compromises stromal cell support of hematopoietic progenitor cells. Reverse-transcriptase–polymerase chain reaction (RT-PCR) analysis revealed that bone marrow stromal cells express 5 FGF receptors (FGFRs) among the 7 known FGFR subtypes. Blocking experiments identified FGFR1 IIIc as the receptor mediating FGF2 inhibition of SDF-1 expression in bone marrow stromal cells. Analysis of the mechanisms underlying FGF2 inhibition of SDF-1 production in bone marrow stromal cells revealed that FGF2 reduces the SDF-1 mRNA content by posttranscriptionally accelerating SDF-1 mRNA decay. Thus, we identify FGF2 as an inhibitor of SDF-1 production in bone marrow stromal cells and a regulator of stromal cell supportive functions for hematopoietic progenitor cells.

Use of Merocyanine 540 for the Isolation of Quiescent, Primitive Human Bone Marrow Hematopoietic Progenitor Cells

1999 ◽  
Vol 8 (2) ◽  
pp. 189-198 ◽  
Author(s):  
Robert E. Pyatt ◽  
Laura L. Jenski ◽  
Ruth Allen ◽  
Ken Cornetta ◽  
Rafat Abonour ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Merocyanine 540

scholarly journals Functional activity of animal bone marrow cells after their treatment with nanocomplexes

2021 ◽  
Vol 29 (2) ◽  
pp. 9-21
Author(s):  
A. M. Goltsev ◽  
T. G. Dubrava ◽  
Yu. O. Gaevska ◽  
N. M. Babenko ◽  
M. O. Bondarovych ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Toxic Effect ◽  
Progenitor Cells ◽  
Functional Activity ◽  
Therapeutic Dose ◽  
Bone Marrow Cells ◽  
Earth Metal ◽  
Hematopoietic Progenitor Cells ◽  
National Academy Of Sciences ◽  
Hematopoietic Progenitor

Background. Previously, the antitumor activity of nanocomplexes (NCs) containing nanoparticles of rare earth metal orthovanadates GdYEuVO4 and cholesterol has been approved when applied in 9:1 ratio (the cells-to-NCs), which can be considered as a conditionally therapeutic dose. Therefore, studying the potential risks of NCs exposure in terms of functional activity of hematopoietic progenitor cells is relevant. Рurpose – determining a toxic effect of NCs on functional activity of hematopoietic cells of bone marrow (BM). Materials and Methods. The study was performed in BM cells of CBA/H mice. Nanocomplexes were synthesized at Institute for Scintillation Materials of the National Academy of Sciences of Ukraine. BM cells with NCs were incubated in the ratios as follows: 9BM:1NCs; 1BM:1NCs; 1BM:9NCs, followed by assessing the number of apoptotic/necrotic cells in BM using FITC Annexin V Apoptosis Detection Kit I (BD, USA) by means of “FACS Calibur” flow cytometer (“BD”, USA). Hematopoietic progenitor cells of BM were functionally evaluated in vivo by determining the content of colony-forming units of the spleen (CFUs) and the number of myelokaryocytes in lethally irradiated recipients on day 8 after administering BM cells, pre-incubated with NCs. Survival of irradiated recipient mice after BM administration was recorded 12 days long. Results and discussion. The dose-dependent effect of functional potential in- hibition for BM hematopoietic progenitor cells under NCs influence has been established. Although, in vitro processing the BM cells with a conditionally therapeutic dose of NCs (9BM:1NCs) before administration to irradiated animal caused remodeling of cell membranes and contributed to apoptotic manifes- tations, but it did not lead to strong changes in their colony-forming potential and did not reduce the number of BM cells in animals if compared with the introduced BM cells without NCs treatment. Increasing the NCs concentration five- and tenfold significantly reduced the colony-forming potential of BM cells, caused BM hypoplasia and a crucial reduction in the survival of recipient animals, indicating possible toxic effects of this compound when administered at high concentrations. Conclusions. The toxic effect of NCs is detected only when certain concen- trations, significantly exceeding the conditionally therapeutic dose previously determined when treating the experimental oncology diseases, are used.

scholarly journals Identification of BCR/ABL-negative primitive hematopoietic progenitor cells within chronic myeloid leukemia marrow

Blood ◽  
1993 ◽  
Vol 81 (3) ◽  
pp. 801-807 ◽  
Author(s):  
T Leemhuis ◽  
D Leibowitz ◽  
G Cox ◽  
R Silver ◽  
EF Srour ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Progenitor Cells ◽  
Myeloid Leukemia ◽  
Chronic Phase ◽  
Polymerase Chain Reaction Analysis ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Hematopoietic Stem

Chronic myeloid leukemia (CML) is a malignant disorder of the hematopoietic stem cell. It has been shown that normal stem cells coexist with malignant stem cells in the bone marrow of patients with chronic-phase CML. To characterize the primitive hematopoietic progenitor cells within CML marrow, CD34+DR- and CD34+DR+ cells were isolated using centrifugal elutriation, monoclonal antibody labeling, and flow cytometric cell sorting. Polymerase chain reaction analysis of RNA samples from these CD34+ subpopulations was used to detect the presence of the BCR/ABL translocation characteristic of CML. The CD34+DR+ subpopulation contained BCR/ABL(+) cells in 11 of 12 marrow samples studied, whereas the CD34+DR- subpopulation contained BCR/ABL(+) cells in 6 of 9 CML marrow specimens. These cell populations were assayed for hematopoietic progenitor cells, and individual hematopoietic colonies were analyzed by PCR for their BCR/ABL status. Results from six patients showed that nearly half of the myeloid colonies cloned from CD34+DR- cells were BCR/ABL(+), although the CD34+DR- subpopulation contained significantly fewer BCR/ABL(+) progenitor cells than either low-density bone marrow (LDBM) or the CD34+DR+ fraction. These CD34+ cells were also used to establish stromal cell-free long-term bone marrow cultures to assess the BCR/ABL status of hematopoietic stem cells within these CML marrow populations. After 28 days in culture, three of five cultures initiated with CD34+DR- cells produced BCR/ABL(-) cells. By contrast, only one of eight cultures initiated with CD34+DR+ cells were BCR/ABL(-) after 28 days. These results indicate that the CD34+DR- subpopulation of CML marrow still contains leukemic progenitor cells, although to a lesser extent than either LDBM or CD34+DR+ cells.

scholarly journals DONOR HEMATOPOIETIC PROGENITOR CELLS IN NONMYELOABLATED RAT RECIPIENTS OF ALLOGENEIC BONE MARROW AND LIVER GRAFTS1

1999 ◽  
Vol 67 (6) ◽  
pp. 833-840 ◽  
Author(s):  
Toshiki Sakamoto ◽  
Qing Ye ◽  
Lina Lu ◽  
Anthony J. Demetris ◽  
Thomas E. Starzl ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Allogeneic Bone Marrow ◽  
Hematopoietic Progenitor Cells ◽  
Allogeneic Bone ◽  
Hematopoietic Progenitor

scholarly journals CD34+ hematopoietic progenitor cells are not a major reservoir of the human immunodeficiency virus

Blood ◽  
1990 ◽  
Vol 76 (7) ◽  
pp. 1281-1286 ◽  
Author(s):  
D von Laer ◽  
FT Hufert ◽  
TE Fenner ◽  
S Schwander ◽  
M Dietrich ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Human Immunodeficiency Virus ◽  
Progenitor Cells ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Aids Patients ◽  
Proviral Dna ◽  
Two Samples ◽  
Immunodeficiency Virus ◽  
Hiv 1

Abstract Hematologic abnormalities occur in the majority of patients with acquired immunodeficiency syndrome (AIDS). Infection of the hematopoietic progenitor cells has been proposed as a potential explanation. In this study, different bone marrow cell populations, including the CD34+ hematopoietic progenitor cells, were purified by a fluorescence-activated cell sorter (FACS) and analyzed for the presence of human immunodeficiency virus-1 (HIV-1) proviral DNA using the polymerase chain reaction. A group of 14 patients with AIDS or AIDS- related complex (ARC) was studied (11 with peripheral blood cytopenias). The CD4+ helper cells in the bone marrow were found positive for HIV-1 DNA in all patients. In contrast, CD34+ progenitor cells were positive in only one patient. Two monocyte samples and two samples of CD4-/CD34- lymphocytes/blasts (mainly B and CD8 lymphocytes) were positive. Proviral DNA could not be detected in granulocytes. FACS analysis showed that the percentage of CD34+ hematopoietic progenitor cells was not altered in the bone marrow of AIDS patients in comparison with the HIV-1 seronegative controls. In contrast, the number of CD4+ lymphocytes was markedly reduced in the bone marrow of AIDS patients. These results show that the hematologic abnormalities in AIDS patients are neither explained by direct infection of the hematopoietic progenitor cells with HIV-1 nor by a depletion of progenitor cells.

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