The CD69 early activation molecule is overexpressed in human bone marrow mast cells from adults with indolent systemic mast cell disease

Abstract An animal model for malignant mastocytosis is described in mice reconstituted with bone marrow cells expressing the v-erbB oncogene. The lethal mast cell disease is characterized by massive infiltration of bone marrow, spleen, and several other visceral organs by connective tissue mast cells, which normally reside in the skin and the peritoneal cavity. As is frequently found in malignant mastocytosis, the v-erbB- induced mast cell disease was accompanied in some primary recipients by an acute myelogenous leukemia (AML) that killed all secondary recipients regardless of whether the AML was already evident in the primary host. The infiltrating mast cells stained strongly positive with berberine sulfate, suggesting that they were terminally differentiated and in vitro they showed only a weak proliferative capacity. The leukemias were clonal but apparently of different origin than the malignant mast cells, implying the transformation of two independent cell populations. Leukemic cells expressed various myeloid- specific markers as well as the B220 antigen, normally associated with the B-cell lineage. However, the Ig heavy chain genes were still in germ line configuration. In culture, these cells proliferated in the absence of exogenous growth factors and had the capacity to differentiate into mature myeloid cells. Preliminary experiments suggest that v-erbB may use parts of a signal transduction pathway normally coupled to the c-kit receptor. The v-erbB-induced malignant mast cell disease should provide a useful animal model for elucidating the cause for malignant mastocytosis in humans and to explore possible therapeutic strategies.

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Immunophenotype of Bone Marrow Mast Cells in Indolent Systemic Mast Cell Disease in Adults

Leukemia & Lymphoma ◽

10.3109/10428199909145725 ◽

1999 ◽

Vol 35 (3-4) ◽

pp. 227-235 ◽

Cited By ~ 37

Author(s):

Luis Escribano ◽

Beatriz Díaz Agustín ◽

Pilar Bravo ◽

Raquel Navalón ◽

Julia Almeida ◽

...

Keyword(s):

Bone Marrow ◽

Mast Cell ◽

Mast Cells ◽

Cell Disease ◽

Mast Cell Disease

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Ultrastructural characterization of basophils and mast cells derived from CD34+ human bone marrow progenitor cells

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010015931x ◽

1990 ◽

Vol 48 (3) ◽

pp. 354-355

Author(s):

J.P. Goff ◽

A. S. Kirshenbaum ◽

J. P. Albert ◽

D. D. Metcalfe

Keyword(s):

Bone Marrow ◽

Mast Cell ◽

Mast Cells ◽

Progenitor Cells ◽

Mononuclear Cells ◽

Bone Marrow Cells ◽

Human Bone ◽

Human Bone Marrow ◽

Human Mast Cell ◽

Mouse Mast Cell

In the mouse, mast cell progenitor cells (Thyl +) have been shown to originate in the bone marrow. In humans, it has been suggested that mast cell progenitors also exist in the bone marrow, are derived from a common stem cell, and mature under cytokine influence in the tissue. Progenitor cells or CD34+ cells comprise approximately 1% of bone marrow mononuclear cells.Previously we have shown that a heterogenous population of human bone marrow cells cultured over agarose surfaces in the presence of rhIL-3 gives rise to basophils and small numbers of mast cells. Cells were identified as basophils based on characteristic morphology, metachromatic staining with Wright-Giemsa and acid toluidine blue, surface IgE as determined by fluorescence and the presence of histamine by o-Phthaldialdehyde condensation. These cells did not stain for the mast cell specific neutral protease, tryptase. Cells identified as mast cells had IgE receptors, contained histamine and were chloroacetate esterase and human mast cell tryptase positive.

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Indolent Systemic Mast Cell Disease in Adults: Immunophenotypic Characterization of Bone Marrow Mast Cells and Its Diagnostic Implications

Blood ◽

10.1182/blood.v91.8.2731.2731_2731_2736 ◽

1998 ◽

Vol 91 (8) ◽

pp. 2731-2736 ◽

Cited By ~ 182

Author(s):

Luis Escribano ◽

Alberto Orfao ◽

Beatriz Dı́az-Agustin ◽

Jesús Villarrubia ◽

Carlos Cerveró ◽

...

Keyword(s):

Bone Marrow ◽

Mast Cell ◽

Mast Cells ◽

Statistical Significance ◽

Normal Subjects ◽

Light Scatter ◽

Cell Disease ◽

Mast Cell Disease ◽

Normal Controls

The aim of the present study was to explore the diagnostic value of the immunophenotypic analysis of bone marrow mast cells (BMMC) in indolent systemic mast cell disease (SMCD) patients. For that purpose, a total of 10 SMCD patients and 19 healthy controls were analyzed. Our results show that BMMC from SMCD are different from normal BMMC with regard to both their light scatter and immunophenotypic characteristics. Accordingly, forward light scatter (FSC), side (90°) light scatter (SSC), and baseline autofluorescence levels were higher in BMMC from indolent SMCD patients than they were in control subjects. From the immunophenotypic point of view, the most striking findings were the constant expression of CD2 (P = .0001), CD25 (P = .0001), and CD35 (P = .06) molecules by BMMC from SMCD patients, markers that were absent from all normal controls. In contrast, CD71, absent in BMMC from indolent SMCD, was positive in BMMC from normal subjects. Although, slight differences between BMMC from SMCD patients and normal controls were found in several other markers, they did not reach statistical significance. In conclusion, our results show that simultaneous assessment of FSC/SSC and reactivity for the CD117, CD2, CD25, CD33, and CD35 forms the basis for the immunophenotypic characterization of BMMC from SMCD in adults and should be integrated with clinical and morphologic studies for the diagnosis of the disease.

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Development of a lethal mast cell disease in mice reconstituted with bone marrow cells expressing the v-erbB oncogene

Blood ◽

10.1182/blood.v79.12.3145.bloodjournal79123145 ◽

1992 ◽

Vol 79 (12) ◽

pp. 3145-3158 ◽

Cited By ~ 9

Author(s):

T von Ruden ◽

S Kandels ◽

T Radaszkiewicz ◽

A Ullrich ◽

EF Wagner

Keyword(s):

Bone Marrow ◽

Animal Model ◽

Mast Cell ◽

Mast Cells ◽

Bone Marrow Cells ◽

Myelogenous Leukemia ◽

Leukemic Cells ◽

Cell Disease ◽

Mast Cell Disease ◽

Marrow Cells

An animal model for malignant mastocytosis is described in mice reconstituted with bone marrow cells expressing the v-erbB oncogene. The lethal mast cell disease is characterized by massive infiltration of bone marrow, spleen, and several other visceral organs by connective tissue mast cells, which normally reside in the skin and the peritoneal cavity. As is frequently found in malignant mastocytosis, the v-erbB- induced mast cell disease was accompanied in some primary recipients by an acute myelogenous leukemia (AML) that killed all secondary recipients regardless of whether the AML was already evident in the primary host. The infiltrating mast cells stained strongly positive with berberine sulfate, suggesting that they were terminally differentiated and in vitro they showed only a weak proliferative capacity. The leukemias were clonal but apparently of different origin than the malignant mast cells, implying the transformation of two independent cell populations. Leukemic cells expressed various myeloid- specific markers as well as the B220 antigen, normally associated with the B-cell lineage. However, the Ig heavy chain genes were still in germ line configuration. In culture, these cells proliferated in the absence of exogenous growth factors and had the capacity to differentiate into mature myeloid cells. Preliminary experiments suggest that v-erbB may use parts of a signal transduction pathway normally coupled to the c-kit receptor. The v-erbB-induced malignant mast cell disease should provide a useful animal model for elucidating the cause for malignant mastocytosis in humans and to explore possible therapeutic strategies.

Download Full-text