Cloning and Characterization of the Novel Chimeric Gene p53/FXR2 in the Acute Megakaryoblastic Leukemia Cell Line CMK11-5

6-[3-adamantyl-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) is a novel compound that represents the prototype of a new class of synthetic retinoids with apoptogenic properties in acute promyelocytic leukemia (APL) and other types of leukemia. In this article, using SCID mice xenografted with APL-derived NB4 cells, we demonstrate that CD437 has significant antileukemic activity in vivo. In addition, we report on the isolation and characterization of an APL cell line (NB4.437r) resistant to CD437. The cell line retains expression of PML-RAR and is approximately 33-fold more resistant than the parental counterpart to the apoptogenic effects of the retinoid. Resistance is relatively specific to CD437 and structural congeners because the NB4.437r cell line is still sensitive to various types of apoptogenic compounds. The CD437-resistant cell line maintains sensitivity to the antiproliferative and apoptotic action of all-trans-retinoic acid, AM580, and fenretinide, though it shows partial resistance to the cytodifferentiating effects of the first 2 compounds. Resistance to CD437 lays upstream of the CD437-induced release of cytochrome c from the mitochondria and the activation of caspase-3, -7, -8, and -9. Furthermore, NB4.437r cells are deficient in the CD437-dependent activation of nuclear NFkb and AP1-binding activities and in the phosphorylation of the protein kinase Akt. In the case of AP1, deficient assembly of the complex is not caused by the lack of activation of the Jun N-terminal kinase (JNK) family of kinases. The novel cell line will be useful in the elucidation of the molecular mechanisms underlying the apoptogenic action of CD437 and structurally related retinoids.

Download Full-text

Isolation and characterization of an acute promyelocytic leukemia cell line selectively resistant to the novel antileukemic and apoptogenic retinoid 6-[3-adamantyl-4-hydroxyphenyl]-2-naphthalene carboxylic acid

Blood ◽

10.1182/blood.v95.8.2672 ◽

2000 ◽

Vol 95 (8) ◽

pp. 2672-2682 ◽

Cited By ~ 27

Author(s):

Isabella Ponzanelli ◽

Maurizio Giannı̀ ◽

Raffaella Giavazzi ◽

Angela Garofalo ◽

Ines Nicoletti ◽

...

Keyword(s):

Carboxylic Acid ◽

Cell Line ◽

Acute Promyelocytic Leukemia ◽

Molecular Mechanisms ◽

Leukemia Cell ◽

Promyelocytic Leukemia ◽

Leukemia Cell Line ◽

The Novel ◽

Isolation And Characterization

Abstract 6-[3-adamantyl-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) is a novel compound that represents the prototype of a new class of synthetic retinoids with apoptogenic properties in acute promyelocytic leukemia (APL) and other types of leukemia. In this article, using SCID mice xenografted with APL-derived NB4 cells, we demonstrate that CD437 has significant antileukemic activity in vivo. In addition, we report on the isolation and characterization of an APL cell line (NB4.437r) resistant to CD437. The cell line retains expression of PML-RAR and is approximately 33-fold more resistant than the parental counterpart to the apoptogenic effects of the retinoid. Resistance is relatively specific to CD437 and structural congeners because the NB4.437r cell line is still sensitive to various types of apoptogenic compounds. The CD437-resistant cell line maintains sensitivity to the antiproliferative and apoptotic action of all-trans-retinoic acid, AM580, and fenretinide, though it shows partial resistance to the cytodifferentiating effects of the first 2 compounds. Resistance to CD437 lays upstream of the CD437-induced release of cytochrome c from the mitochondria and the activation of caspase-3, -7, -8, and -9. Furthermore, NB4.437r cells are deficient in the CD437-dependent activation of nuclear NFkb and AP1-binding activities and in the phosphorylation of the protein kinase Akt. In the case of AP1, deficient assembly of the complex is not caused by the lack of activation of the Jun N-terminal kinase (JNK) family of kinases. The novel cell line will be useful in the elucidation of the molecular mechanisms underlying the apoptogenic action of CD437 and structurally related retinoids.

Download Full-text

Characterization of two novel sublines established from a human megakaryoblastic leukemia cell line transfected with p210BCR-ABL

Leukemia Research ◽

10.1016/s0145-2126(99)00179-4 ◽

2000 ◽

Vol 24 (4) ◽

pp. 289-297 ◽

Cited By ~ 5

Author(s):

Ellin Berman ◽

Suresh Jhanwar ◽

Mary McBride ◽

Annabel Strife ◽

David Wisniewski ◽

...

Keyword(s):

Cell Line ◽

Leukemia Cell ◽

Leukemia Cell Line ◽

Megakaryoblastic Leukemia

Download Full-text

Characterization of prostaglandin and thromboxane receptors expressed on a megakaryoblastic leukemia cell line, MEG-01s

Blood ◽

10.1182/blood.v78.9.2328.bloodjournal7892328 ◽

1991 ◽

Vol 78 (9) ◽

pp. 2328-2336 ◽

Cited By ~ 1

Author(s):

T Watanabe ◽

Y Yatomi ◽

S Sunaga ◽

I Miki ◽

A Ishii ◽

...

Keyword(s):

Cell Line ◽

Binding Sites ◽

Leukemia Cell ◽

Leukemia Cell Line ◽

Camp Production ◽

Megakaryoblastic Leukemia ◽

Ic50 Values ◽

Thromboxane Receptors ◽

And Function

MEG-01s, an established human megakaryoblastic leukemia cell line, exhibited specific high-affinity binding sites for [3H]iloprost, a stable prostaglandin (PG) I2 analogue, for [3H]SQ-29548, a stable thromboxane (TX) A2 antagonist and, for [3H]PGE2/PGE1, but not for [3H]PGD2. In the MEG-01s cells, iloprost/PGI2, or PGE1 stimulated cAMP production with ED50 values practically identical to the IC50 values for the [3H] iloprost binding. STA2 and U46619, TXA2/PGH2 agonists, PGE2/PGE1, iloprost/PGI2, and thrombin elevated the intracellular concentrations of Ca2+ ([Ca2+]i), as determined by Fura-2 fluorescence signals. Elevation of [Ca2+]i by PGE2/PGE1 and iloprost, but not that by TX-agonists or thrombin, was totally dependent on the presence of extracellular Ca2+. This effect by PGE2/PGE1 was partially inhibited by prior treatment of the cells with islet-activating protein (IAP), while that by TX-agonists or by PGI2/iloprost was not affected. We tentatively conclude from these results that: (1) MEG-01s cells express (a) PGI2/PGE1 receptor(s) coupled to adenylate cyclase and Ca2+ influx, a TXA2/PGH2 receptor coupled to the phosphatidylinositol-turnover-Ca2+ system, and the PGE2/PGE1 receptor coupled to Ca2+ influx; (2) the receptors for TXA2/PGH2 and iloprost and those for PGE2/PGE1 and thrombin are coupled to IAP-insensitive and IAP-sensitive GTP-binding proteins, respectively, and function in a different manner to elevate [Ca2+]i. Thus, the MEG-01s cell line is a pertinent model for studying eicosanoid receptor-mediated signal transduction in platelet/megakaryocyte systems.

Download Full-text

Characterization of prostaglandin and thromboxane receptors expressed on a megakaryoblastic leukemia cell line, MEG-01s

Blood ◽

10.1182/blood.v78.9.2328.2328 ◽

1991 ◽

Vol 78 (9) ◽

pp. 2328-2336 ◽

Cited By ~ 33

Author(s):

T Watanabe ◽

Y Yatomi ◽

S Sunaga ◽

I Miki ◽

A Ishii ◽

...

Keyword(s):

Cell Line ◽

Binding Sites ◽

Leukemia Cell ◽

Leukemia Cell Line ◽

Camp Production ◽

Megakaryoblastic Leukemia ◽

Ic50 Values ◽

Thromboxane Receptors ◽

And Function

Abstract MEG-01s, an established human megakaryoblastic leukemia cell line, exhibited specific high-affinity binding sites for [3H]iloprost, a stable prostaglandin (PG) I2 analogue, for [3H]SQ-29548, a stable thromboxane (TX) A2 antagonist and, for [3H]PGE2/PGE1, but not for [3H]PGD2. In the MEG-01s cells, iloprost/PGI2, or PGE1 stimulated cAMP production with ED50 values practically identical to the IC50 values for the [3H] iloprost binding. STA2 and U46619, TXA2/PGH2 agonists, PGE2/PGE1, iloprost/PGI2, and thrombin elevated the intracellular concentrations of Ca2+ ([Ca2+]i), as determined by Fura-2 fluorescence signals. Elevation of [Ca2+]i by PGE2/PGE1 and iloprost, but not that by TX-agonists or thrombin, was totally dependent on the presence of extracellular Ca2+. This effect by PGE2/PGE1 was partially inhibited by prior treatment of the cells with islet-activating protein (IAP), while that by TX-agonists or by PGI2/iloprost was not affected. We tentatively conclude from these results that: (1) MEG-01s cells express (a) PGI2/PGE1 receptor(s) coupled to adenylate cyclase and Ca2+ influx, a TXA2/PGH2 receptor coupled to the phosphatidylinositol-turnover-Ca2+ system, and the PGE2/PGE1 receptor coupled to Ca2+ influx; (2) the receptors for TXA2/PGH2 and iloprost and those for PGE2/PGE1 and thrombin are coupled to IAP-insensitive and IAP-sensitive GTP-binding proteins, respectively, and function in a different manner to elevate [Ca2+]i. Thus, the MEG-01s cell line is a pertinent model for studying eicosanoid receptor-mediated signal transduction in platelet/megakaryocyte systems.

Download Full-text

Author response for "Establishment and characterization of a DOT1L inhibitor‐sensitive human acute monocytic leukemia cell line YBT‐5 with a novel KMT2A‐MLLT3 fusion"

10.1002/hon.2686/v2/response1 ◽

2019 ◽

Author(s):

Zhenhua Wang ◽

Yongjin Shi ◽

Huihui Liu ◽

Zeyin Liang ◽

Qiang Zhu ◽

...

Keyword(s):

Cell Line ◽

Leukemia Cell ◽

Author Response ◽

Leukemia Cell Line ◽

Acute Monocytic Leukemia ◽

Monocytic Leukemia

Download Full-text

Establishment and characterization of an STI571-resistant human myelogenous leukemia cell line, SR-1

Cancer Genetics and Cytogenetics ◽

10.1016/j.cancergencyto.2004.01.009 ◽

2004 ◽

Vol 154 (1) ◽

pp. 52-56 ◽

Cited By ~ 1

Author(s):

Hyuk-Chan Kwon ◽

Sung-Hyun Kim ◽

Jae-Seok Kim ◽

Hoon Han ◽

Mee Sook Roh ◽

...

Keyword(s):

Cell Line ◽

Leukemia Cell ◽

Myelogenous Leukemia ◽

Leukemia Cell Line

Download Full-text

Outside-In Signaling of Soluble and Solid-Phase Fibrinogen Through Integrin ΙΙbβ3 Is Different and Cooperative With Each Other in a Megakaryoblastic Leukemia Cell Line, CMK

Blood ◽

10.1182/blood.v92.4.1277 ◽

1998 ◽

Vol 92 (4) ◽

pp. 1277-1286 ◽

Cited By ~ 19

Author(s):

Yumi Tohyama ◽

Kaoru Tohyama ◽

Misao Tsubokawa ◽

Momoyo Asahi ◽

Yataro Yoshida ◽

...

Keyword(s):

Cell Adhesion ◽

Signaling Pathways ◽

Cell Line ◽

Tyrosine Phosphorylation ◽

Solid Phase ◽

Leukemia Cell ◽

Leukemia Cell Line ◽

Megakaryoblastic Leukemia ◽

Integrin Β3 ◽

Coated Plate

Abstract The function and the outside-in signaling pathways of IIbβ3 were examined in relation to cell adhesion using a megakaryoblastic leukemia cell line, CMK. After 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment, the cells adhered to the culture plate and underwent megakaryocytic differentiation with expression of IIbβ3. Binding of soluble fibrinogen to the cells via IIbβ3 was dependent on cell adhesion. Cell detaching reduced the affinity of this integrin for soluble fibrinogen, although its surface expression was almost unchanged. In contrast, detached cells became tightly adherent to the fibrinogen-coated plate (solid-phase fibrinogen). The same ligand, fibrinogen, present either in soluble or solid-phase form, triggered differential signaling pathways mediated by IIbβ3. By the stimulation with soluble fibrinogen, Syk was tyrosine-phosphorylated but FAK was dephosphorylated, whereas solid-phase fibrinogen promptly caused tyrosine phosphorylation of FAK followed by delayed phosphorylation of Syk. In addition, the binding of soluble fibrinogen to the cells adherent to fibrinogen-coated plate resulted in tyrosine phosphorylation of integrin β3 and a complex formation of integrin β3 with Syk. This implies the cooperation of both soluble and solid-phase fibrinogen-mediated signaling pathways. © 1998 by The American Society of Hematology.

Download Full-text