scholarly journals The combined effects of IL-3 and PSC 833 on daunorubicin- and mitoxantrone cytotoxicity in two growth factor-dependent leukemic cell lines

Leukemia ◽  
1997 ◽  
Vol 11 (5) ◽  
pp. 680-686 ◽  
Author(s):  
J Asschert ◽  
E de Vries ◽  
D van der Kolk ◽  
M Müller ◽  
E Vellenga
Keyword(s):  
Growth Factor ◽  
Cell Lines ◽  
Leukemic Cell ◽  
Combined Effects ◽  
Leukemic Cell Lines ◽  
Psc 833

scholarly journals Unlike its Paralog LEDGF/p75, HRP-2 Is Dispensable for MLL-R Leukemogenesis but Important for Leukemic Cell Survival

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 192
Author(s):  
Siska Van Belle ◽  
Sara El Ashkar ◽  
Kateřina Čermáková ◽  
Filip Matthijssens ◽  
Steven Goossens ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Survival ◽  
Cell Lines ◽  
Protein Interactions ◽  
Leukemic Cell ◽  
Related Protein ◽  
Histone Tails ◽  
Knockout Mouse Model ◽  
Leukemic Cell Lines

HDGF-related protein 2 (HRP-2) is a member of the Hepatoma-Derived Growth Factor-related protein family that harbors the structured PWWP and Integrase Binding Domain, known to associate with methylated histone tails or cellular and viral proteins, respectively. Interestingly, HRP-2 is a paralog of Lens Epithelium Derived Growth Factor p75 (LEDGF/p75), which is essential for MLL-rearranged (MLL-r) leukemia but dispensable for hematopoiesis. Sequel to these findings, we investigated the role of HRP-2 in hematopoiesis and MLL-r leukemia. Protein interactions were investigated by co-immunoprecipitation and validated using recombinant proteins in NMR. A systemic knockout mouse model was used to study normal hematopoiesis and MLL-ENL transformation upon the different HRP-2 genotypes. The role of HRP-2 in MLL-r and other leukemic, human cell lines was evaluated by lentiviral-mediated miRNA targeting HRP-2. We demonstrate that MLL and HRP-2 interact through a conserved interface, although this interaction proved less dependent on menin than the MLL-LEDGF/p75 interaction. The systemic HRP-2 knockout mice only revealed an increase in neutrophils in the peripheral blood, whereas the depletion of HRP-2 in leukemic cell lines and transformed primary murine cells resulted in reduced colony formation independently of MLL-rearrangements. In contrast, primary murine HRP-2 knockout cells were efficiently transformed by the MLL-ENL fusion, indicating that HRP-2, unlike LEDGF/p75, is dispensable for the transformation of MLL-ENL leukemogenesis but important for leukemic cell survival.

Constitutive Activation of the JAK2/STAT5 Signal Transduction Pathway Correlates With Growth Factor Independence of Megakaryocytic Leukemic Cell Lines

Blood ◽  
1999 ◽  
Vol 93 (7) ◽  
pp. 2369-2379 ◽  
Author(s):  
Richard Y. Liu ◽  
Chun Fan ◽  
Roy Garcia ◽  
Richard Jove ◽  
Kenneth S. Zuckerman
Keyword(s):  
Signal Transduction ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Dna Binding ◽  
Cell Lines ◽  
Leukemic Cell ◽  
Constitutive Activation ◽  
Leukemic Cell Lines ◽  
Binding Factor ◽  
Hel Cells

Abstract The factor-independent Dami/HEL and Meg-01 and factor-dependent Mo7e leukemic cell lines were used as models to investigate JAK/STAT signal transduction pathways in leukemic cell proliferation. Although Dami/HEL and Meg-01 cell proliferation in vitro was independent of and unresponsive to exogenous cytokines including granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), IL-6, thrombopoietin (TPO), and tumor necrosis factor- (TNF-), the growth of Mo7e cells was dependent on hematopoietic growth factors. When these cell lines were cultured in medium without cytokines, a constitutively activated STAT-like DNA-binding factor was detected in nuclear extracts from both Dami/HEL and Meg-01 cells. However, the STAT-like factor was not detectable in untreated Mo7e cells, but was activated transiently in Mo7e cells in response to cytokine treatments. The constitutively activated and cytokine-induced STAT-like DNA-binding factor in these three cell lines was identified as STAT5 by oligonucleotide competition gel mobility assays and by specific anti-STAT antibody gel supershift assays. Constitutive activation of JAK2 also was detected in the factor-independent cell lines, but not in Mo7e cells without cytokine exposure. Meg-01 cells express a p185 BCR/ABL oncogene, which may be responsible for the constitutive activation of STAT5. Dami/HEL cells do not express the BCR/ABL oncogene, but increased constitutive phosphorylation of Raf-1 oncoprotein was detected. In cytokine bioassays using growth factor-dependent Mo7e and TF-1 cells as targets, conditioned media from Dami/HEL and Meg-01 cells did not show stimulatory effects on cell proliferation. Our results indicate that the constitutive activation of JAK2/STAT5 correlates with the factor-independent growth of Dami/HEL and Meg-01 cells. The constitutive activation of JAK2/STAT5 in Dami/HEL cells is triggered by a mechanism other than autocrine cytokines or the BCR/ABL oncoprotein.

Constitutive Activation of the JAK2/STAT5 Signal Transduction Pathway Correlates With Growth Factor Independence of Megakaryocytic Leukemic Cell Lines

Blood ◽  
1999 ◽  
Vol 93 (7) ◽  
pp. 2369-2379 ◽  
Author(s):  
Richard Y. Liu ◽  
Chun Fan ◽  
Roy Garcia ◽  
Richard Jove ◽  
Kenneth S. Zuckerman
Keyword(s):  
Signal Transduction ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Dna Binding ◽  
Cell Lines ◽  
Leukemic Cell ◽  
Constitutive Activation ◽  
Leukemic Cell Lines ◽  
Binding Factor ◽  
Hel Cells

The factor-independent Dami/HEL and Meg-01 and factor-dependent Mo7e leukemic cell lines were used as models to investigate JAK/STAT signal transduction pathways in leukemic cell proliferation. Although Dami/HEL and Meg-01 cell proliferation in vitro was independent of and unresponsive to exogenous cytokines including granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), IL-6, thrombopoietin (TPO), and tumor necrosis factor- (TNF-), the growth of Mo7e cells was dependent on hematopoietic growth factors. When these cell lines were cultured in medium without cytokines, a constitutively activated STAT-like DNA-binding factor was detected in nuclear extracts from both Dami/HEL and Meg-01 cells. However, the STAT-like factor was not detectable in untreated Mo7e cells, but was activated transiently in Mo7e cells in response to cytokine treatments. The constitutively activated and cytokine-induced STAT-like DNA-binding factor in these three cell lines was identified as STAT5 by oligonucleotide competition gel mobility assays and by specific anti-STAT antibody gel supershift assays. Constitutive activation of JAK2 also was detected in the factor-independent cell lines, but not in Mo7e cells without cytokine exposure. Meg-01 cells express a p185 BCR/ABL oncogene, which may be responsible for the constitutive activation of STAT5. Dami/HEL cells do not express the BCR/ABL oncogene, but increased constitutive phosphorylation of Raf-1 oncoprotein was detected. In cytokine bioassays using growth factor-dependent Mo7e and TF-1 cells as targets, conditioned media from Dami/HEL and Meg-01 cells did not show stimulatory effects on cell proliferation. Our results indicate that the constitutive activation of JAK2/STAT5 correlates with the factor-independent growth of Dami/HEL and Meg-01 cells. The constitutive activation of JAK2/STAT5 in Dami/HEL cells is triggered by a mechanism other than autocrine cytokines or the BCR/ABL oncoprotein.

scholarly journals Growth factor requirements of childhood acute leukemia: establishment of GM-CSF-dependent cell lines

Blood ◽  
1987 ◽  
Vol 70 (1) ◽  
pp. 192-199 ◽  
Author(s):  
B Lange ◽  
M Valtieri ◽  
D Santoli ◽  
D Caracciolo ◽  
F Mavilio ◽  
...  
Keyword(s):  
Growth Factor ◽  
Acute Leukemia ◽  
Cell Lines ◽  
Leukemic Cell ◽  
Media Analysis ◽  
Leukemic Cells ◽  
Gm Csf ◽  
Leukemic Cell Lines ◽  
Dependent Cell ◽  
Childhood Acute Leukemia

Eight permanent cell lines were established from cells of 50 consecutive patients with childhood acute leukemia. Three cell lines required growth factor-containing conditioned media. Analysis using blocking antisera and recombinant granulocytic macrophage (GM) colony- stimulating factor (CSF) identified GM-CSF as a growth factor required to establish the latter three cell lines and necessary for their continuous proliferation in chemically defined medium. Two of the GM- CSF-dependent cell lines were derived from patients with undifferentiated T- and a biphenotypic B-myelomonocytic leukemia, which suggests that GM-CSF might maintain proliferation of leukemias originating from immature progenitor cells. Cytogenetic analysis indicated that all established leukemic cell lines were aneuploid, with six lines containing chromosomal alterations related to those observed in the leukemic cells of the patient. Two patients did not have an abnormal clone identified in the marrow but did yield an aneuploid cell line. These studies indicate that GM-CSF-dependent leukemic cell lines can be established in a fraction of childhood leukemia. These cell lines lend themselves to studies aimed at the evaluation in vitro of the role of growth factors in controlling proliferation and differentiation of leukemic cells.

scholarly journals Growth factor requirements of childhood acute leukemia: establishment of GM-CSF-dependent cell lines

Blood ◽  
1987 ◽  
Vol 70 (1) ◽  
pp. 192-199 ◽  
Author(s):  
B Lange ◽  
M Valtieri ◽  
D Santoli ◽  
D Caracciolo ◽  
F Mavilio ◽  
...  
Keyword(s):  
Growth Factor ◽  
Acute Leukemia ◽  
Cell Lines ◽  
Leukemic Cell ◽  
Media Analysis ◽  
Leukemic Cells ◽  
Gm Csf ◽  
Leukemic Cell Lines ◽  
Dependent Cell ◽  
Childhood Acute Leukemia

Abstract Eight permanent cell lines were established from cells of 50 consecutive patients with childhood acute leukemia. Three cell lines required growth factor-containing conditioned media. Analysis using blocking antisera and recombinant granulocytic macrophage (GM) colony- stimulating factor (CSF) identified GM-CSF as a growth factor required to establish the latter three cell lines and necessary for their continuous proliferation in chemically defined medium. Two of the GM- CSF-dependent cell lines were derived from patients with undifferentiated T- and a biphenotypic B-myelomonocytic leukemia, which suggests that GM-CSF might maintain proliferation of leukemias originating from immature progenitor cells. Cytogenetic analysis indicated that all established leukemic cell lines were aneuploid, with six lines containing chromosomal alterations related to those observed in the leukemic cells of the patient. Two patients did not have an abnormal clone identified in the marrow but did yield an aneuploid cell line. These studies indicate that GM-CSF-dependent leukemic cell lines can be established in a fraction of childhood leukemia. These cell lines lend themselves to studies aimed at the evaluation in vitro of the role of growth factors in controlling proliferation and differentiation of leukemic cells.

Repositioning of Difluorinated Propanediones as Inhibitors of Histone Methyltransferases and their Biological Evaluation in Human Leukemic Cell Lines

2019 ◽  
Vol 18 (13) ◽  
pp. 1892-1899 ◽  
Author(s):  
Tanushree Pal ◽  
Asmita Sharda ◽  
Bharat Khade ◽  
C. Sinha Ramaa ◽  
Sanjay Gupta
Keyword(s):  
Cell Lines ◽  
Physiological Role ◽  
Leukemic Cell ◽  
Docking Studies ◽  
Biological Evaluation ◽  
Leukemic Cell Lines ◽  
Histone Lysine ◽  
Histone Lysine Methyltransferase ◽  
Subsequent Decrease

Background: At present, ‘pharmaco-epigenomics’ constitutes the hope in cancer treatment owing to epigenetic deregulation- a reversible process and playing a role in malignancy. Objective: Chemotherapy has many limitations like host-tissue toxicity, drug resistance. Hence, it is imperative to unearth targets to better treat cancer. Here, we intend to repurpose a set of our previously synthesized difluorinated Propanediones (PR) as Histone lysine Methyltransferase inhibitors (HMTi). Methods: The cell lines of leukemic origin viz. histiocytic lymphoma (U937) and acute T-cell leukemia (JURKAT) were treated with PR-1 to 7 after docking studies with active pocket of HMT. The cell cycle analysis, in vitro methylation and cell proliferation assays were carried out to delineate their physiological role. Results: A small molecule PR-4, at 1 and 10µM, has shown to alter the methylation of histone H3 and H4 in both cell lines. Also, treatment shows an increase in G2/M population and a subsequent decrease in the G0/G1 population in U937. In JURKAT, an increase in both G2/M and S phase population was observed. The sub-G1 population showed a steady rise with increase in dose and prolonged time intervals in U937 and JURKAT cell lines. In SRB assay, the PR showed a cell growth of 42.6 and 53.4% comparable to adriamycin; 44.5 and 53.2% in U937 and JURKAT, respectively. The study suggests that PR-4 could emerge as a potential HMT inhibitor. Conclusion: The molecule PR-4 could be a lead in developing more histone lysine methyltransferases inhibitors with potential to be pro-apoptotic agents.

A novel peptide isolated from garlic shows anticancer effect against leukemic cell lines via interaction with Bcl‐2 family proteins

2021 ◽  
Vol 97 (5) ◽  
pp. 1017-1028
Author(s):  
Karunaithas Rasaratnam ◽  
Chanin Nantasenamat ◽  
Narumon Phaonakrop ◽  
Sittiruk Roytrakul ◽  
Dalina Tanyong
Keyword(s):  
Cell Lines ◽  
Leukemic Cell ◽  
Anticancer Effect ◽  
Leukemic Cell Lines
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