Costunolide promotes imatinib-induced apoptosis in chronic myeloid leukemia cells via the Bcr/Abl-Stat5 pathway

2018 ◽  
Vol 32 (9) ◽  
pp. 1764-1769 ◽  
Author(s):  
Hong Cai ◽  
Xiaolin He ◽  
Chunhui Yang
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Leukemia Cells ◽  
Induced Apoptosis

Bcr-Abl-Mediated Suppression of Normal Hematopoiesis in Chronic Myeloid Leukemia: Involvement of a Modified Form of NGAL.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2869-2869
Author(s):  
Hui Lin ◽  
Xiaohong Leng ◽  
Tong Sun ◽  
Giuseppe Monaco ◽  
Clifton Stephens ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Hematopoietic Cells ◽  
K562 Cells ◽  
Soft Agar ◽  
Leukemia Cells ◽  
Active Process ◽  
Culture Studies ◽  
Induced Apoptosis

Abstract The BCR-ABL oncogene plays an essential role in chronic myeloid leukemia (CML). In NOD/scid mice injected with soft agar clones of a human CML cell line (K562), we observed a leukemia syndrome involving not only leukemia but also a severe reduction of normal mouse hematopoiesis (Lin et al., Oncogene, 2001). Some of these mice died of a wasting syndrome that involved suppression of hematopoiesis without extensive tumor cell invasion of the spleen and marrow. In CML patients, since normal hematopoietic cells in marrow and spleen are replaced with proliferating leukemic blasts, we postulate that this is an active process mediated by the leukemia cells. The lipocalin 24p3 is secreted by mouse hematopoietic cells deprived of IL-3, resulting in apoptosis induction in a variety of hematopoietic cells including bone marrow cells (Devireddy et al., Science, 2001). We found that BCR-ABL+ mouse hematopoietic cells induce a persistent secretion of a modified form of 24p3 (21 kDa). Co-culture studies show that BCR-ABL+ cells induced apoptosis in BCR-ABL negative cells. Importantly, BCR-ABL+ hematopoietic cells are resistant to apoptosis under the same conditions. Conditioned medium (CM) from BCR-ABL+ cells expressing anti-sense/siRNA 24p3 or CM mixed with 24p3 antibody have reduced apoptotic activity for target cells. We also found that the expression of the Bcr-Abl oncoprotein and its tyrosine kinase are required for induction of 24p3 expression. Leukemic mice induced by BCR-ABL+ cells expressing anti-sense/siRNA 24p3 have increased levels of normal hematopoiesis (marrow and spleen erythropoiesis and blood platelet levels) and reduced invasion of leukemia cells in marrow and spleen tissues, but the leukemia cells readily invade liver and the abdomen as ascites (Lin et al, Oncogene, 2005). These findings indicate that suppression of normal hematopoiesis in BCR-ABL induced leukemia is an active process involving the apoptotic factor 24p3, raising the possibility that similar factors are involved in BCR-ABL+ CML patients. We have found that the K562 clones (Lin et al. 2001) have enhanced expression of NGAL (neutrophil gelatinase-associated lipocalin, human homologue of 24p3) transcripts compared to uncloned K562 cells. We generated additional soft agar K562 clones, each with different expression levels of NGAL transcripts. NOD/scid mice injected with the clone (C5) of K562 cell line expressing a high level of NGAL had severe depression of hematopoiesis and significantly shorter survival time as compared with mice injected with parental K562 cells and a clone (C6) expressing a low level of NGAL. Co-culture studies showed that the C5 K562 clone also induced apoptosis in BCR-ABL negative cells. We detected two glycosylated forms of NGAL/24p3 migrating at 24 kDa and 21 kDa on SDS-PAGE. The 21 kDa form is the major form in CM from mouse BCR-ABL+ cells and K562 clones. Our preliminary data with CML patient samples showed that levels of 21 kDa NGAL protein in bone marrow fluid correlated with BCR-ABL/ABL ratio. Further studies with more patient samples are ongoing to confirm the role of NGAL in suppressing normal hematopoiesis in CML patients and to determine the structural change(s) that leads to the modified form of 24p3/NGAL secreted by CML cells.

scholarly journals STAT pathway in the regulation of zoledronic acid-induced apoptosis in chronic myeloid leukemia cells

2013 ◽  
Vol 67 (6) ◽  
pp. 527-532 ◽  
Author(s):  
Hatice Demet Kiper ◽  
Burcin Tezcanli Kaymaz ◽  
Aysun Adan Gokbulut ◽  
Nur Selvi ◽  
Cigir Biray Avci ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Leukemia Cells ◽  
Induced Apoptosis ◽  
Stat Pathway

scholarly journals Activation of c-Jun N-Terminal Kinase Mediates Tanshinone IIA-Induced Apoptosis in KBM-5 Chronic Myeloid Leukemia Cells

2013 ◽  
Vol 36 (2) ◽  
pp. 208-214 ◽  
Author(s):  
Sun-Mi Yun ◽  
Soo-Jin Jeong ◽  
Ji-Hyun Kim ◽  
Ji Hoon Jung ◽  
Hyo-Jung Lee ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Tanshinone Iia ◽  
Leukemia Cells ◽  
Induced Apoptosis

Potential anti-MDR agents based on the podophyllotoxin scaffold: synthesis and antiproliferative activity evaluation against chronic myeloid leukemia cells by activating MAPK signaling pathways

RSC Advances ◽  
2016 ◽  
Vol 6 (4) ◽  
pp. 2895-2903 ◽  
Author(s):  
Lei Zhang ◽  
Zeguo Zhang ◽  
Jing Wang ◽  
Yongzheng Chen ◽  
Fan Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Chronic Myeloid Leukemia ◽  
Antiproliferative Activity ◽  
Myeloid Leukemia ◽  
Mapk Signaling ◽  
Leukemia Cells ◽  
M Cell ◽  
Cycle Arrest ◽  
Induced Apoptosis ◽  
Mapk Signaling Pathways

Compound 9k exhibited excellent cytotoxicity, induced apoptosis and G2/M cell cycle arrest, downregulated Pgp expression and up-regulated the expression of p-ERK1/2, p-JNK and p-p38 in K562/ADR cells.

scholarly journals Anti-rheumatic agent auranofin induced apoptosis in chronic myeloid leukemia cells resistant to imatinib through both Bcr/Abl-dependent and -independent mechanisms

Oncotarget ◽  
2014 ◽  
Vol 5 (19) ◽  
pp. 9118-9132 ◽  
Author(s):  
Xin Chen ◽  
Xianping Shi ◽  
Chong Zhao ◽  
Xiaofen Li ◽  
Xiaoying Lan ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Leukemia Cells ◽  
Induced Apoptosis

scholarly journals Sphingosine kinase-1 is a downstream regulator of imatinib-induced apoptosis in chronic myeloid leukemia cells

Leukemia ◽  
2008 ◽  
Vol 22 (5) ◽  
pp. 971-979 ◽  
Author(s):  
E Bonhoure ◽  
A Lauret ◽  
D J Barnes ◽  
C Martin ◽  
B Malavaud ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Sphingosine Kinase ◽  
Leukemia Cells ◽  
Sphingosine Kinase 1 ◽  
Induced Apoptosis
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