Establishment and characterization of a human leukemic cell line with megakaryocytic features: Dependency on granulocyte-macrophage colony-stimulating factor, interleukin 3, or erythropoietin for growth and survival

Norio Komatsu, Hiromitsu Nakauchi, Akiyoshi Miwa, Toshiki Ishihara, Mitsuoki Eguchi, Masaaki Moroi, Masayuki Okada, Yuko Sato, Hideho Wada, Yoshihito Yawata, Toshio Suda, Yasusada Miura

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Abstract

A new human leukemia cell line with megakaryocytic features, designated UT-7, was established from the bone marrow of a patient with acute megakaryoblastic leukemia. Surface marker analysis revealed that the majority of the cells reacted with monoclonal antibodies against platelet glycoprotein Ib (CD42b), glycoprotein IIb/IIIa (CD41a), MY 7 (CD13), MY 9 (CD33), and glycophorin A antigens. Cytogenetic analysis showed a human male near-tetraploid karyotype with a modal chromosome number of 92-96. Flow cytometry-derived DNA histograms demonstrated that the majority of the cells spontaneously contained 4 N DNA ploidy levels. Ultrastructural study showed that platelet peroxidase activity was weakly positive but myeloperoxidase activity was negative. Ferritin and θ-granule, which have been used as ultrastructural markers for the erythroid lineage, could not be detected. In response to phorbol myristate acetate, platelet factor 4 and β-thromboglobulin, which were specifically synthesized in the process of megakaryocyte maturation, dramatically increased in UT-7 cells. This was accompanied by an increase in cell size, ploidy level, platelet peroxidase activity, and the surface density of glycoprotein IIb/IIIa antigen. These findings suggest that UT-7 is a new leukemic cell line with megakaryocytic features and with the potential to differentiate into cells with more mature megakaryocytic properties in response to phorbol myristate acetate. This cell line showed strict dependency on interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor, or erythropoietin. The maximal effective doses of IL-3, granulocyte-macrophage colony-stimulating factor, and erythropoietin for proliferation in liquid culture were 10 units/ml, 1 ng/ml, and 1 unit/ml, respectively. These concentrations were comparable to the doses that maximally stimulate the clonal growth of normal hemopoietic cells. IL-6 could stimulate the proliferation of UT-7 cells but not maintain the line in long-term culture. UT-7 cells may be a useful model for (a) the analysis of gene regulation of megakaryocytic maturation-associated proteins expressed in the process of megakaryocytic differentiation and (b) the study of signal transduction of hemopoietic factors associated with megakaryocytopoiesis.

Original languageEnglish
Pages (from-to)341-348
Number of pages8
JournalCancer Research
Volume51
Issue number1
Publication statusPublished - 1991 Jan 1

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Interleukin-3
Granulocyte-Macrophage Colony-Stimulating Factor
Erythropoietin
Cell Line
Survival
Growth
Peroxidase
Platelet Glycoprotein GPIIb-IIIa Complex
Ploidies
Tetradecanoylphorbol Acetate
Blood Platelets
Leukemia, Megakaryoblastic, Acute
Platelet Glycoprotein GPIb-IX Complex
Thrombopoiesis
Glycophorin
Platelet Membrane Glycoproteins
Platelet Factor 4
Antigens
Tetraploidy
Megakaryocytes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Establishment and characterization of a human leukemic cell line with megakaryocytic features : Dependency on granulocyte-macrophage colony-stimulating factor, interleukin 3, or erythropoietin for growth and survival. / Komatsu, Norio; Nakauchi, Hiromitsu; Miwa, Akiyoshi; Ishihara, Toshiki; Eguchi, Mitsuoki; Moroi, Masaaki; Okada, Masayuki; Sato, Yuko; Wada, Hideho; Yawata, Yoshihito; Suda, Toshio; Miura, Yasusada.

In: Cancer Research, Vol. 51, No. 1, 01.01.1991, p. 341-348.

Research output: Contribution to journalArticle

Komatsu, N, Nakauchi, H, Miwa, A, Ishihara, T, Eguchi, M, Moroi, M, Okada, M, Sato, Y, Wada, H, Yawata, Y, Suda, T & Miura, Y 1991, 'Establishment and characterization of a human leukemic cell line with megakaryocytic features: Dependency on granulocyte-macrophage colony-stimulating factor, interleukin 3, or erythropoietin for growth and survival', Cancer Research, vol. 51, no. 1, pp. 341-348.
Komatsu, Norio ; Nakauchi, Hiromitsu ; Miwa, Akiyoshi ; Ishihara, Toshiki ; Eguchi, Mitsuoki ; Moroi, Masaaki ; Okada, Masayuki ; Sato, Yuko ; Wada, Hideho ; Yawata, Yoshihito ; Suda, Toshio ; Miura, Yasusada. / Establishment and characterization of a human leukemic cell line with megakaryocytic features : Dependency on granulocyte-macrophage colony-stimulating factor, interleukin 3, or erythropoietin for growth and survival. In: Cancer Research. 1991 ; Vol. 51, No. 1. pp. 341-348.
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AU - Nakauchi, Hiromitsu

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AU - Ishihara, Toshiki

AU - Eguchi, Mitsuoki

AU - Moroi, Masaaki

AU - Okada, Masayuki

AU - Sato, Yuko

AU - Wada, Hideho

AU - Yawata, Yoshihito

AU - Suda, Toshio

AU - Miura, Yasusada

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N2 - A new human leukemia cell line with megakaryocytic features, designated UT-7, was established from the bone marrow of a patient with acute megakaryoblastic leukemia. Surface marker analysis revealed that the majority of the cells reacted with monoclonal antibodies against platelet glycoprotein Ib (CD42b), glycoprotein IIb/IIIa (CD41a), MY 7 (CD13), MY 9 (CD33), and glycophorin A antigens. Cytogenetic analysis showed a human male near-tetraploid karyotype with a modal chromosome number of 92-96. Flow cytometry-derived DNA histograms demonstrated that the majority of the cells spontaneously contained 4 N DNA ploidy levels. Ultrastructural study showed that platelet peroxidase activity was weakly positive but myeloperoxidase activity was negative. Ferritin and θ-granule, which have been used as ultrastructural markers for the erythroid lineage, could not be detected. In response to phorbol myristate acetate, platelet factor 4 and β-thromboglobulin, which were specifically synthesized in the process of megakaryocyte maturation, dramatically increased in UT-7 cells. This was accompanied by an increase in cell size, ploidy level, platelet peroxidase activity, and the surface density of glycoprotein IIb/IIIa antigen. These findings suggest that UT-7 is a new leukemic cell line with megakaryocytic features and with the potential to differentiate into cells with more mature megakaryocytic properties in response to phorbol myristate acetate. This cell line showed strict dependency on interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor, or erythropoietin. The maximal effective doses of IL-3, granulocyte-macrophage colony-stimulating factor, and erythropoietin for proliferation in liquid culture were 10 units/ml, 1 ng/ml, and 1 unit/ml, respectively. These concentrations were comparable to the doses that maximally stimulate the clonal growth of normal hemopoietic cells. IL-6 could stimulate the proliferation of UT-7 cells but not maintain the line in long-term culture. UT-7 cells may be a useful model for (a) the analysis of gene regulation of megakaryocytic maturation-associated proteins expressed in the process of megakaryocytic differentiation and (b) the study of signal transduction of hemopoietic factors associated with megakaryocytopoiesis.

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