Nucleolar Asynchrony in Blastic Cells of Acute Myeloid Leukemia — Possible Connection with the Drug Resistance?

1999 ◽  
pp. 36-41
Author(s):  
K. Smetana ◽  
L. Rosa ◽  
I. Jirásková ◽  
P. K. Chan ◽  
D. Lesáková ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Acute Myeloid

c-Myc plays part in drug resistance mediated by bone marrow stromal cells in acute myeloid leukemia

2015 ◽  
Vol 39 (1) ◽  
pp. 92-99 ◽  
Author(s):  
Bing Xia ◽  
Chen Tian ◽  
Shanqi Guo ◽  
Le Zhang ◽  
Dandan Zhao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Drug Resistance ◽  
Acute Myeloid Leukemia ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Myeloid Leukemia ◽  
Marrow Stromal Cells ◽  
Acute Myeloid

scholarly journals CD9, a potential leukemia stem cell marker, regulates drug resistance and leukemia development in acute myeloid leukemia

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yongliang Liu ◽  
Guiqin Wang ◽  
Jiasi Zhang ◽  
Xue Chen ◽  
Huailong Xu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Drug Resistance ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Stem Cell Marker ◽  
Hematopoietic Stem ◽  
Chemotherapy Drugs ◽  
And Migration ◽  
Acute Myeloid

Abstract Background Leukemia stem cells (LSCs) are responsible for the initiation, progression, and relapse of acute myeloid leukemia (AML). Therefore, a therapeutic strategy targeting LSCs is a potential approach to eradicate AML. In this study, we aimed to identify LSC-specific surface markers and uncover the underlying mechanism of AML LSCs. Methods Microarray gene expression data were used to investigate candidate AML-LSC-specific markers. CD9 expression in AML cell lines, patients with AML, and normal donors was evaluated by flow cytometry (FC). The biological characteristics of CD9-positive (CD9+) cells were analyzed by in vitro proliferation, chemotherapeutic drug resistance, migration, and in vivo xenotransplantation assays. The molecular mechanism involved in CD9+ cell function was investigated by gene expression profiling. The effects of alpha-2-macroglobulin (A2M) on CD9+ cells were analyzed with regard to proliferation, drug resistance, and migration. Results CD9, a cell surface protein, was specifically expressed on AML LSCs but barely detected on normal hematopoietic stem cells (HSCs). CD9+ cells exhibit more resistance to chemotherapy drugs and higher migration potential than do CD9-negative (CD9−) cells. More importantly, CD9+ cells possess the ability to reconstitute human AML in immunocompromised mice and promote leukemia growth, suggesting that CD9+ cells define the LSC population. Furthermore, we identified that A2M plays a crucial role in maintaining CD9+ LSC stemness. Knockdown of A2M impairs drug resistance and migration of CD9+ cells. Conclusion Our findings suggest that CD9 is a new biomarker of AML LSCs and is a promising therapeutic target.

Long noncoding RNAs: A novel insight in the leukemogenesis and drug resistance in acute myeloid leukemia

2021 ◽  
Author(s):  
Anuradha Kirtonia ◽  
Milad Ashrafizadeh ◽  
Ali Zarrabi ◽  
Kiavash Hushmandi ◽  
Amirhossein Zabolian ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Acute Myeloid

scholarly journals Silencing long non-coding RNA XIST suppresses drug resistance in acute myeloid leukemia through down-regulation of MYC by elevating microRNA-29a expression

2020 ◽  
Vol 26 (1) ◽  
Author(s):  
Chong Wang ◽  
Lingling Li ◽  
Mengya Li ◽  
Weiqiong Wang ◽  
Yanfang Liu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Drug Resistance ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Bone Marrow Cells ◽  
Cellular Viability ◽  
Down Regulation ◽  
Acute Myeloid

Abstract Background Long non-coding RNAs (lncRNAs) are biomarkers participating in multiple disease development including acute myeloid leukemia (AML). Here, we investigated molecular mechanism of X Inactive-Specific Transcript (XIST) in regulating cellular viability, apoptosis and drug resistance in AML. Methods XIST, miR-29a and myelocytomatosis oncogene (MYC) expression in AML bone marrow cells collected from 62 patients was evaluated by RT-qPCR and Western blot analysis. Besides, the relationship among XIST, miR-29a and MYC was analyzed by dual luciferase reporter assay, RIP, and RNA pull down assays. AML KG-1 cells were treated with anti-tumor drug Adriamycin. The role of XIST/miR-29a/MYC in cellular viability, apoptosis and drug resistance in AML was accessed via gain- and loss-of-function approaches. At last, we evaluated role of XIST/miR-29a/MYC on tumorigenesis in vivo. Results XIST and MYC were up-regulated, and miR-29a was down-regulated in AML bone marrow cells. Silencing XIST inhibited cellular activity and drug resistance but promoted cellular apoptosis of KG-1 cells by down-regulating MYC. XIST inhibited miR-29a expression to up-regulate MYC. Moreover, silencing XIST inhibited tumorigenesis of AML cells in vivo. Conclusions Overall, down-regulation of XIST decreased MYC expression through releasing the inhibition on miR-29a, thereby reducing drug resistance, inhibiting viability and promoting apoptosis of AML cells.

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