Vav3 collaborates with p190-BCR-ABL in lymphoid progenitor leukemogenesis, proliferation, and survival

Chang, Kyung Hee; Sánchez-Aguilera, Abel; Shen, Shuhong; Sengupta, Amitava; Madhu, Malav; Ficker, Ashley; Dunn, Susan; Kuenzi, Ashley M.; Arnett, Jorden; Santho, Rebecca A.; Agirre, Xabier; Perentesis, John P.; Deininger, Michael W.; Zheng, Yi; Bustelo, Xosé R.; Williams, David A.; Cancelas, José A.

doi:10.1182/blood-2011-06-361709

Cited by 43 publications

(58 citation statements)

References 52 publications

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“…The PIM protein belongs to the Ser̸Thr protein kinase family, is involved in multiple signal transduction pathways and is highly expressed in several types of tumors, including lymphoma (19). In this study, the expression variation trends of BAX and Bcl-xL in Raji and Jurkat cells following treatment with As 2 S 2 were in accordance with previous studies (20)(21)(22), with the difference that BAX in Jurkat cells was reduced to a lower level compared to the control group (P<0.01). Kang et al (23) conducted a study on human cervical cancer cells and reported that the translocation of BAX and the phosphorylation of Bcl-2 were associated with cell apoptosis and the increased level of mitochondrial BAX coexisted with no or minimal change in the total amount of BAX.…”

Section: Discussionsupporting

confidence: 77%

Effects of arsenic sulfide (As2S2) on B and T lymphoma cell lines and possible underlying mechanisms

Liu

et al. 2013

Biomedical Reports

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Abstract. Lymphoma is a hematological malignancy that originates from lymph nodes and lymphoid tissues and is divided into Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), based on its histopathological characteristics. The aim of this study was to investigate the effects of arsenic sulfide (As 2 S 2 ), the main ingredient of realgar, on the proliferation and apoptosis of the Raji B-cell lymphoma and Jurkat T-cell lymphoma lines, comparing the sensitivity between the two cell lines and investigating the possible underlying mechanisms. The two lymphoma cell lines were cultured in vitro, using different concentrations of As 2 S 2 for different time periods. The cell proliferation was detected using the Cell Counting kit-8 (CCK-8). Apoptosis was assessed via flow cytometry. Expression levels of the apoptosis-associated genes [Homo sapiens Bcl-2-associated X protein (BAX), Homo sapiens B-cell CLL/lymphoma 2 (Bcl-2), Homo sapiens Bcl-2-like protein 1 (BCL2L1, Bcl-xL), Homo sapiens v-myc myelocytomatosis viral oncogene homolog (avian) (MYC, c-Myc) and Homo sapiens pim-1 oncogene (PIM)] were measured via the reverse transcription polymerase chain reaction (RT-PCR) method. The results demonstrated that As 2 S 2 inhibited proliferation and induced apoptosis in the two lymphoma cell lines in a time-and concentration-dependent manner, with the Raji cells being more sensitive to As 2 S 2 compared to Jurkat cells. As 2 S 2 may also alter the expression levels of different apoptosis-associated genes, with the alterations of the mRNA expression levels being different between Raji and Jurkat cells. These findings indicated that As 2 S 2 may inhibit the proliferation and promote the apoptosis of non-Hodgkin lymphoma (NHL) cell lines and that B-cell lymphoma cell lines are more sensitive compared to T-cell lymphoma cell lines. The possible underlying mechanism is that As 2 S 2 alters the expression levels of the apoptosis-associated genes and activates apoptosis-associated signaling pathways.

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Section: Discussionsupporting

confidence: 77%

Effects of arsenic sulfide (As2S2) on B and T lymphoma cell lines and possible underlying mechanisms

Liu

et al. 2013

Biomedical Reports

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“…Of the three VAV proteins, VAV3 reportedly plays an important role in tumor development and metastasis [33]. Previous reports demonstrated that VAV3 overexpression was associated with poor prognosis in gastric cancer patients [34], and VAV3 knockdown impaired carcinogenesis in leukemia and gastric cancer [34,35]; however, VAV3 expression in ovarian cancer has not yet been reported. In the present study, we revealed that VAV3 was overexpressed in OSCs, and VAV3 regulated CSC activation and cancer cell proliferation by spheroid-forming and colony-forming assays.…”

Section: Discussionmentioning

confidence: 99%

VAV3 Overexpressed in Cancer Stem Cells Is a Poor Prognostic Indicator in Ovarian Cancer Patients

Kwon

Kim

Jeong

et al. 2015

Stem Cells and Development

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Ovarian carcinoma is a highly lethal malignancy due to frequent relapse and drug resistance. Cancer stem cells (CSCs) are thought to contribute significantly to disease relapse and drug resistance. In this study, a subpopulation of CSCs of ovarian carcinoma was isolated and the genes differentially expressed in these cells were identified to characterize CSCs and to find candidate biomarkers. Ovarian carcinoma cells from patients were primarily cultured, and spheroid-forming cells (SFCs) were isolated. The characteristic genes of SFCs were identified through cDNA microarray and validation by quantitative real-time polymerase chain reaction and immunohistochemistry, and the association of their expression with clinicopathologic parameters was analyzed. GSC (4.26-fold), VAV3 (7.05-fold), FOXA2 (12.06-fold), LEF1 (17.26-fold), COMP (21.33-fold), GRIN2A (9.36-fold), CD86 (23.14-fold), PYY (4.18-fold), NKX3-2 (10.35-fold), and PDK4 (74.26-fold) were significantly upregulated in SFCs compared with parental cancer cells. With validation for human ovarian carcinomas, LEF1, PYY, NKX3-2, and WNT3A were significantly upregulated in chemoresistant cancers compared with chemosensitive cancers. Overexpression of LEF1, VAV3, and NKX3-2 was significantly associated with distant metastasis by immunohistochemistry. VAV3 overexpression was an independent poor survival indicator (hazard ratio=15.27, P<0.05) by multivariate Cox analysis. The further functional assay revealed that VAV3 knockdown regulated CSC activation and ovarian cancer cell proliferation and sensitized paclitaxel (PTX)-resistant cancer cells to PTX treatment. Taken together, we identified by high-throughput analysis of CSCs that VAV3 overexpression is a novel biomarker for poor prognosis and survival in ovarian carcinoma.

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“…20 The results of longer-term follow-up (median, 2 years) in both of the COMFORT studies indicated that ruxolitinib treatment confers a survival advantage over placebo and best available therapy. 27,28 …”

Section: Ruxolitinibmentioning

confidence: 99%

Ruxolitinib: An Oral Janus Kinase 1 and Janus Kinase 2 Inhibitor in the Management of Myelofibrosis

Verstovšek

2013

Postgraduate Medicine

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Myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET) are referred to as the classic Philadelphia chromosome (BCR-ABL1)-negative myeloproliferative neoplasms. Although each has distinct pathologic features, all 3 display alterations in Janus kinase (JAK) signal transduction activator of transcription signaling. Myelofibrosis is the most serious of the 3, associated with shortened survival (median survival, 5–7 years); bone marrow failure with anemia; progressive splenomegaly; and chronic, burdensome symptoms, including fatigue, night sweats, itching, abdominal discomfort, loss of appetite/early satiety, unintentional weight loss, and bone, chest, and abdominal pain. Treatments for MF have been mainly palliative, with the exception of allogeneic stem cell transplantation, which, although potentially curative, is feasible only in a small subpopulation of patients. In November 2011, ruxolitinib, an inhibitor of JAK1 and JAK2, was approved by the US Food and Drug Administration for the treatment of intermediate- or high-risk MF, including primary MF, post-PV MF, and post-ET MF. In clinical trials, ruxolitinib was shown to reduce spleen volume and improve MF-related symptoms and quality-of-life measures. Evidence also suggests that ruxolitinib therapy has a survival advantage over placebo and best available therapy. Thrombocytopenia and anemia were the most common adverse events with treatment. Ongoing trials are assessing the efficacy and safety of ruxolitinib therapy in patients with PV and ET.

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Vav3 collaborates with p190-BCR-ABL in lymphoid progenitor leukemogenesis, proliferation, and survival

Cited by 43 publications

References 52 publications

Effects of arsenic sulfide (As2S2) on B and T lymphoma cell lines and possible underlying mechanisms

Effects of arsenic sulfide (As2S2) on B and T lymphoma cell lines and possible underlying mechanisms

VAV3 Overexpressed in Cancer Stem Cells Is a Poor Prognostic Indicator in Ovarian Cancer Patients

Ruxolitinib: An Oral Janus Kinase 1 and Janus Kinase 2 Inhibitor in the Management of Myelofibrosis

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