Incidence and prognostic impact of ASXL2 mutations in adult acute myeloid leukemia patients with t(8;21)(q22;q22): a study of the German-Austrian AML Study Group

Jahn, Nikolaus; Agrawal, Mridul; Bullinger, Lars; Weber, Daniela; Corbacioglu, Andrea; Vi, Gaidzik; Schmalbrock, Laura K.; Thol, Felicitas; Heuser, Michael; Krauter, Jürgen; Göhring, Gudrun; Kündgen, Andrea; Fiedler, Walter; Wattad, Mohammed; Held, Gerhard; Ch, Köhne; Ha, Horst; Lübbert, Michael; Ganser, Arnold; Rf, Schlenk; Döhner, Hartmut; Döhner, Konstanze; Paschka, Peter

doi:10.1038/leu.2017.18

Cited by 18 publications

(15 citation statements)

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“…Studies show that ASXL2 acts as an epigenetic regulator by recruiting a multicomb repressor complex (PRC), which activate the DUB and regulate the cell proliferation (10). Nowadays, abnormal expression of ASXL2 has been reported in more and more different types of tumors, and ASXL2 is known to cause poor prognosis in tumor patients (9)(10)(11). However, the prognostic value and clinical signi cance of ASXL2 in CRC have not been reported at home and abroad.…”

Section: Discussionmentioning

confidence: 99%

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ASXL2 promotes colorectal cancer tumorigenesis by inducing cell proliferation

Cui¹,

Yang²,

Wang³

et al. 2020

Preprint

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Background: Colorectal cancer is one of the most common malignant tumors worldwide. ASXL2 is an enhancer of trithorax and polycomb gene, which have been proved to act in many tumor types. The role of ASXL2 in the occurrence and development of tumors have been extensively studied in recent years. However the relationship between ASXL2 and the prognosis of CRC is still unclear.Methods: In this study, quantitative real-time polymerase chain reaction (qRT-PCR), Western blot analysis and immunohistochemistry (IHC) were used to examine the expression of ASXL2 in CRC tissues. Cells were transfected with siRNAs or lentivirus to regulate the expression of ASXL2. The effects of ASXL2 on proliferation of CRC cells were determined by CCK8 assay.Results: This study demonstrated that ASXL2 was significantly more expressed in CRC specimens relative to the normal adjacent tissues. The upregulation of ASXL2 was related to advanced clinical stages. Patients who exhibited high expression levels of ASXL2 had poorer overall survival, whereas those with low expression of ASXL2 survived longer. Multivariate Cox regression analysis revealed ASXL2 expression could be considered as an independent prognostic factor for CRC. Inhibition or overexpression of ASXL2 markedly influenced the proliferation of CRC cells.Conclusion: These results showed that ASXL2 could induce cell proliferation which is associated with poor prognosis of CRC patients and might be a new therapeutic target for CRC.

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Section: Discussionmentioning

confidence: 99%

“…Notably, homologous gene, ASXL1 and ASXL2 are positive regulators of trithorax and Polycomb(ETP) genes. Both of which encode essential transcriptional and epigenetic regulatory proteins in the course of important developmental stages (9)(10)(11)(12)(13). Compared with ASXL1, there is less research on the function of ASXL2.…”

Section: Introductionmentioning

confidence: 99%

ASXL2 promotes colorectal cancer tumorigenesis by inducing cell proliferation

Cui¹,

Yang²,

Wang³

et al. 2020

Preprint

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“…Notably, as homologous genes, ASXL1 and ASXL2 are positive regulators of trithorax and Polycomb (ETP) genes, both encode essential transcriptional and epigenetic regulatory proteins involved in important developmental stages. [9][10][11][12][13] Compared with that of ASXL1, ASXL2 function has been less studied. Studies have shown the potential roles of ASXL2 in cardiac function, adipogenesis and osteoclastogenesis.…”

Section: Introductionmentioning

confidence: 99%

<p>Elevated Expression of ASXL2 is Associated with Poor Prognosis in Colorectal Cancer by Enhancing Tumorigenesis and Inducing Cell Proliferation</p>

Cui¹,

Yang²,

Wang³

et al. 2020

CMAR

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Colorectal cancer is one of the most common malignant tumors worldwide. ASXL2 is an enhancer of the trithorax and polycomb genes, which have been proven to act in many tumor types. The role of ASXL2 in the occurrence and development of tumors has been extensively studied in recent years. However, the relationship between ASXL2 and the prognosis of CRC is still unclear. Materials and Methods: In this study, quantitative real-time polymerase chain reaction (qRT-PCR), Western blot analysis and immunohistochemistry (IHC) were used to examine the expression of ASXL2 in CRC tissues. Cells were transfected with siRNAs or lentivirus to regulate the expression of ASXL2. The effects of ASXL2 on the proliferation of CRC cells were determined by CCK8 assay. Results: This study demonstrated that ASXL2 was significantly more highly expressed in CRC specimens than in normal adjacent tissues. The upregulation of ASXL2 was related to advanced clinical stage. Patients who exhibited high expression levels of ASXL2 had poorer overall survival, whereas those with low expression of ASXL2 survived longer. Multivariate Cox regression analysis revealed that ASXL2 expression could be considered an independent prognostic factor for CRC. Inhibition or overexpression of ASXL2 markedly influenced the proliferation of CRC cells. Conclusion: These results showed that ASXL2 could induce cell proliferation, which was associated with poor prognosis of CRC patients, suggesting that ASXL2 might be a new therapeutic target for CRC.

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“…Although they share similar biological effects like repression of CBF target genes and clinical characteristics including a favorable prognosis [10], t(8;21)(q22;q22.1) and inv(16)(p13.1q22) AML differ in regard to cooccurring mutations. For example, mutations in ASXL1 and ASXL2 occur at a high frequency in AML with t(8;21) (q22;q22.1) but are absent in AML with an inv (16) (p13.1q22) implying that they selectively cooperate with AML1-ETO [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Functional characterization of BRCC3 mutations in acute myeloid leukemia with t(8;21)(q22;q22.1)

et al. 2019

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BRCA1/BRCA2-containing complex 3 (BRCC3) is a Lysine 63-specific deubiquitinating enzyme (DUB) involved in inflammasome activity, interferon signaling, and DNA damage repair. Recurrent mutations in BRCC3 have been reported in myelodysplastic syndromes (MDS) but not in de novo AML. In one of our recent studies, we found BRCC3 mutations selectively in 9/191 (4.7%) cases with t(8;21)(q22;q22.1) AML but not in 160 cases of inv(16)(p13.1q22) AML. Clinically, AML patients with BRCC3 mutations had an excellent outcome with an event-free survival of 100%. Inactivation of BRCC3 by CRISPR/Cas9 resulted in improved proliferation in t(8;21)(q22;q22.1) positive AML cell lines and together with expression of AML1-ETO induced unlimited self-renewal in mouse hematopoietic progenitor cells in vitro. Mutations in BRCC3 abrogated its deubiquitinating activity on IFNAR1 resulting in an impaired interferon response and led to diminished inflammasome activity. In addition, BRCC3 inactivation increased release of several cytokines including G-CSF which enhanced proliferation of AML cell lines with t(8;21)(q22;q22.1). Cell lines and primary mouse cells with inactivation of BRCC3 had a higher sensitivity to doxorubicin due to an impaired DNA damage response providing a possible explanation for the favorable outcome of BRCC3 mutated AML patients.

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Incidence and prognostic impact of ASXL2 mutations in adult acute myeloid leukemia patients with t(8;21)(q22;q22): a study of the German-Austrian AML Study Group

Cited by 18 publications

References 15 publications

ASXL2 promotes colorectal cancer tumorigenesis by inducing cell proliferation

ASXL2 promotes colorectal cancer tumorigenesis by inducing cell proliferation

<p>Elevated Expression of ASXL2 is Associated with Poor Prognosis in Colorectal Cancer by Enhancing Tumorigenesis and Inducing Cell Proliferation</p>

Functional characterization of BRCC3 mutations in acute myeloid leukemia with t(8;21)(q22;q22.1)

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