in vitro studies with melphalan and pediatric neoplastic and normal bone marrow cells

Abstract Although it has been demonstrated that lymphokine-activated killer (LAK) cells kill tumor cells in a selective way without being toxic to a variety of normal cells, contradictory results exist about the possible toxicity of natural killer (NK) and LAK cells for hematopoietic progenitor cells. Therefore, the cytolytic activity and growth inhibitory effects of LAK cells on normal bone marrow progenitor cells and the ability of LAK cells to eliminate neoplastic hematopoietic cells from populations of bone marrow cells in vitro was studied. The results of these experiments show the following: (1) LAK cells have little cytolytic activity against normal bone marrow cells; (2) normal bone marrow cells fail to cold target compete for the killing of the hematopoietic tumor cell lines K562 and HL60 or freshly frozen acute myelocytic leukemia (AML) blast cells by LAK cells; (3) LAK cells inhibit the growth of K562 and HL60 to more than 90% in clonogenic assays; (4) LAK cells have no inhibitory effect on hematopoietic progenitor growth in CFU-GM (colony-forming unit- granulocytes, macrophages), CFU-E (colony-forming unit-erythrocytes), BFU-E (burst-forming units-erythrocytes), or CFU-GEMM (colony-forming unit-granulocytes, erythrocytes, macrophages, megakaryocytes) assays. These results indicate that LAK cells have low toxicity for normal bone marrow and that LAK activity against tumor cells is not adversely affected by the presence of normal bone marrow cells. The differences in cytolysis and growth inhibition of neoplastic hematopoietic cells and hematopoietic progenitor cells by LAK cells in vitro could create a therapeutic index that might allow the use of LAK cells for cleansing of the autologous bone marrow graft and for adjuvant therapy in combination with autologous bone marrow transplantation without compromising the reconstitution of the bone marrow in the host.

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Factor-dependent in vitro growth of human normal bone marrow-derived basophil-like cells.

Journal of Experimental Medicine ◽

10.1084/jem.158.3.857 ◽

1983 ◽

Vol 158 (3) ◽

pp. 857-871 ◽

Cited By ~ 39

Author(s):

K Tadokoro ◽

B M Stadler ◽

A L De Weck

Keyword(s):

Bone Marrow ◽

T Cells ◽

Bone Marrow Cells ◽

Interleukin 2 ◽

Nonspecific Esterase ◽

Ionophore A23187 ◽

Normal Bone Marrow ◽

Normal Bone ◽

Marrow Cells

A factor(s) present in supernatants from lectin-stimulated peripheral blood mononuclear cells promoted the production of basophil-like cells in liquid cultures of normal human bone marrow cells. The cultured basophil-like cells had lobulated or round nuclei, and the cytoplasmic granules stained metachromatically with toluidine blue and azurophilic with Giemsa. 20% of the metachromatically staining cells were peroxidase positive but not positive for nonspecific esterase. The histamine content was 0.5-2 pg/cell. The basophil-like cells released histamine upon challenge with calcium ionophore A23187 but not with compound 48/80. They also released histamine with anti-IgE when passively sensitized with human myeloma IgE. The development of basophil-like cells was promoted in a dose-dependent fashion by a factor(s) in the conditioned medium. Blocking of cell proliferation with hydroxyurea or X irradiation inhibited the development of basophil-like cells. The production of the factor was dependent on the presence of T cells. The factor was different from interleukin 2 and its molecular weight was estimated to be 25,000-40,000 by gel filtration on a Sephacryl S-200 column. Thus, human basophil-like cells derived from normal bone marrow cells can grow and differentiate in vitro under the regulation of T cells.

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Toxicity of cytostatic drugs to normal bone marrow cells in vitro

Cancer Chemotherapy and Pharmacology ◽

10.1007/s002800050779 ◽

1998 ◽

Vol 42 (1) ◽

pp. 17-23 ◽

Cited By ~ 12

Author(s):

Britt Sundman-Engberg ◽

Ulf Tidefelt ◽

Christer Paul

Keyword(s):

Bone Marrow ◽

Bone Marrow Cells ◽

Normal Bone Marrow ◽

Cytostatic Drugs ◽

Normal Bone ◽

Marrow Cells

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Lymphokine-activated killer cells selectively kill tumor cells in bone marrow without compromising bone marrow stem cell function in vitro

Blood ◽

10.1182/blood.v74.1.354.bloodjournal741354 ◽

1989 ◽

Vol 74 (1) ◽

pp. 354-360

Author(s):

MR van den Brink ◽

PJ Voogt ◽

WA Marijt ◽

SA van Luxemburg-Heys ◽

JJ van Rood ◽

...

Keyword(s):

Bone Marrow ◽

Tumor Cells ◽

Bone Marrow Cells ◽

Lak Cells ◽

Normal Bone Marrow ◽

Hematopoietic Progenitor ◽

Colony Forming Unit ◽

Normal Bone ◽

Marrow Cells

Although it has been demonstrated that lymphokine-activated killer (LAK) cells kill tumor cells in a selective way without being toxic to a variety of normal cells, contradictory results exist about the possible toxicity of natural killer (NK) and LAK cells for hematopoietic progenitor cells. Therefore, the cytolytic activity and growth inhibitory effects of LAK cells on normal bone marrow progenitor cells and the ability of LAK cells to eliminate neoplastic hematopoietic cells from populations of bone marrow cells in vitro was studied. The results of these experiments show the following: (1) LAK cells have little cytolytic activity against normal bone marrow cells; (2) normal bone marrow cells fail to cold target compete for the killing of the hematopoietic tumor cell lines K562 and HL60 or freshly frozen acute myelocytic leukemia (AML) blast cells by LAK cells; (3) LAK cells inhibit the growth of K562 and HL60 to more than 90% in clonogenic assays; (4) LAK cells have no inhibitory effect on hematopoietic progenitor growth in CFU-GM (colony-forming unit- granulocytes, macrophages), CFU-E (colony-forming unit-erythrocytes), BFU-E (burst-forming units-erythrocytes), or CFU-GEMM (colony-forming unit-granulocytes, erythrocytes, macrophages, megakaryocytes) assays. These results indicate that LAK cells have low toxicity for normal bone marrow and that LAK activity against tumor cells is not adversely affected by the presence of normal bone marrow cells. The differences in cytolysis and growth inhibition of neoplastic hematopoietic cells and hematopoietic progenitor cells by LAK cells in vitro could create a therapeutic index that might allow the use of LAK cells for cleansing of the autologous bone marrow graft and for adjuvant therapy in combination with autologous bone marrow transplantation without compromising the reconstitution of the bone marrow in the host.

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