High expression of Musashi-2 indicates poor prognosis in adult B-cell acute lymphoblastic leukemia

Mu, Qitian; Wang, Yungui; Chen, Bing; Qian, W.; Meng, Haitao; Tong, Hongyan; Chen, Feifei; Ma, Qiuling; Ni, Wanmao; Chen, Sai‐Juan; Jin, Jie

doi:10.1016/j.leukres.2013.05.012

Cited by 33 publications

(36 citation statements)

References 32 publications

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“…Msi2 expression was negatively Msi2 promotes bladder cancer metastasis via JAK2/STAT3 pathway C Yang et al associated with AML patients outcome, 21 while the expression of NUMB, which was negatively regulated by Msi2 both in vitro and in vivo, 19 was not associated with overall survival in AML patients. 22 Mu et al 23 reported that high Msi2 expression could indicate poor prognosis in adult B-cell acute lymphoblastic leukemia. Recently, He et al unraveled the association of Msi2 expression and prognosis in patients with solid tumor.…”

Section: Discussionmentioning

confidence: 99%

Musashi-2 promotes migration and invasion in bladder cancer via activation of the JAK2/STAT3 pathway

Yang

Zhang

Wang

et al. 2016

Laboratory Investigation

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Musashi-2 (Msi2) is considered to have a crucial role in regulating various key cellular functions. However, the clinical significance and biological role of Msi2 in bladder cancer remains unknown. We examined the expression of Msi2 in bladder cancer cell lines in 167 clinical samples and the biological role of Msi2 in bladder cancer cells. Western blotting was used to investigate the possible mechanism of Msi2-induced migration and invasion in bladder cancer. Msi2 was significantly upregulated in bladder cancer cells and tissues compared with normal bladder urothelial cells and tissues. Immunohistochemical analysis revealed high expression of Msi2 in 57 of 167 (34.1%) bladder cancer specimens. Statistical analysis showed a significant correlation of Msi2 expression with advanced clinical stage, lymph node metastasis, and poor prognosis. Overexpression and ablation of Msi2 promoted and inhibited, respectively, the migration and invasion of bladder cancer cells. Furthermore, we found that Msi2 activated the JAK2/STAT3 pathway and promoted expression of genes downstream of JAK2/STAT3 in bladder cancer. This study demonstrates that Msi2 can induce bladder cancer cell migration and invasion by activating the JAK2/STAT3 pathway, and that Msi2 may be a valuable prognostic biomarker for bladder cancer patients.Laboratory Investigation (2016) 96, 950-958;

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Section: Discussionmentioning

confidence: 99%

Musashi-2 promotes migration and invasion in bladder cancer via activation of the JAK2/STAT3 pathway

Yang

Zhang

Wang

et al. 2016

Laboratory Investigation

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“…The MSI family has been demonstrated to be dysregulated in cancer in a variety of tumors including in the brain, prostate, breast, and colon [7, 23–25]. MSI2 is mainly expressed in the hematopoietic system and it is an important modulator of proliferation and differentiation in normal hematopoietic stem cells whereas its overexpression has been related to myeloid [3, 11] and lymphoid malignancies [12]. …”

Section: Discussionmentioning

confidence: 99%

“…In addition to its role in aggressive solid tumors [5], MSI2 fusions have been found in several patients with blast crisis Chronic Myeloid Leukemia (CML-BC), where chromosomal translocations fused MSI2 and HOXA9 [10]. Recent studies have reported that MSI2 overexpression occurs in a variety of hematopoietic malignancies including CML-BC, AML and B-Cell Acute Lymphoblastic Leukemia, and can contribute as a negative prognostic marker [3, 11, 12]. Moreover, recent studies have demonstrated a functional role in which MSI2 can maintain self-renewal and control of hematopoietic differentiation in human myeloid leukemia cell lines [3].…”

Section: Introductionmentioning

confidence: 99%

A 1536-Well Fluorescence Polarization Assay to Screen for Modulators of the MUSASHI Family of RNA-Binding Proteins

Minuesa¹,

Antczak²,

Shum³

et al. 2014

CCHTS

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RNA-binding proteins (RBPs) can act as stem cell modulators and oncogenic drivers, but have been largely ignored by the pharmaceutical industry as potential therapeutic targets for cancer. The MUSASHI (MSI) family has recently been demonstrated to be an attractive clinical target in the most aggressive cancers. Therefore, the discovery and development of small molecule inhibitors could provide a novel therapeutic strategy. In order to find novel compounds with MSI RNA binding inhibitory activity, we have developed a fluorescence polarization (FP) assay and optimized it for high throughput screening (HTS) in a 1536-well microtiter plate format. Using a chemical library of 6,208 compounds, we performed pilot screens, against both MSI1 and MSI2, leading to the identification of 7 molecules for MSI1, 15 for MSI2 and 5 that inhibited both. A secondary FP dose-response screen validated 3 MSI inhibitors with IC50 below 10μM. Out of the 25 compounds retested in the secondary screen only 8 demonstrated optical interference due to high fluorescence. Utilizing a SYBR-based RNA electrophoresis mobility shift assay (EMSA), we further verified MSI inhibition of the top 3 compounds. Surprisingly, even though several aminoglycosides were present in the library, they failed to demonstrate MSI inhibitor activity challenging the concept that these compounds are pan-active against RBPs. In summary, we have developed an in vitro strategy to identify MSI specific inhibitors using an FP HTS platform, which will facilitate novel drug discovery for this class of RBPs.

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“…Other genetic alterations resulting in MSI2 overexpression are observed in blast crisis chronic myelogenous leukemia (CML-BC), which harbors chromosomal translocations that fuse MSI2 with HOXA9 and, most recently, MSI2 with TTC40 (11,12). MSI2 expression levels can predict survival in B cell acute lymphoid leukemia (B-ALL) (13), and patients with higher MSI2 expression in CML-BC have been shown to have worse prognosis (14,15). These findings suggest that increased expression of MSI2 may predict aggressiveness in a variety of cancers.…”

Section: Introductionmentioning

confidence: 99%

Musashi2 sustains the mixed-lineage leukemia–driven stem cell regulatory program

Park¹,

Gönen²,

Vu³

et al. 2015

J. Clin. Invest.

116

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High expression of Musashi-2 indicates poor prognosis in adult B-cell acute lymphoblastic leukemia

Cited by 33 publications

References 32 publications

Musashi-2 promotes migration and invasion in bladder cancer via activation of the JAK2/STAT3 pathway

Musashi-2 promotes migration and invasion in bladder cancer via activation of the JAK2/STAT3 pathway

A 1536-Well Fluorescence Polarization Assay to Screen for Modulators of the MUSASHI Family of RNA-Binding Proteins

Musashi2 sustains the mixed-lineage leukemia–driven stem cell regulatory program

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