Higher HOPX expression is associated with distinct clinical and biological features and predicts poor prognosis in
            <i>de novo</i>
            acute myeloid leukemia

Lin, Chien‐Chin; Hsu, Yueh-Chwen; Li, Yi-Hung; Kuo, Yu-Mei; Hou, Hsin‐An; Lan, Keng-Hsueh; Chen, Tsung-Chih; Tzeng, Yi-Shiuan; Kuo, Yi-Yi; Kao, Chein-Jun; Chuang, Po-Han; Tseng, Mei‐Hsuan; Chiu, Yu‐Chiao; Chou, Wen‐Chien; Tien, Hwei‐Fang

doi:10.3324/haematol.2016.161257

Cited by 38 publications

(35 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…10 Since stemness of leukemia cells is a crucial factor of resistance to chemotherapy, it is reasonable that the expression profile of these LSC genes has significant impact on prognosis of AML patients. 5,10,13,14,25,26 MDS and AML are both myeloid malignancies rising from stem/progenitor cells, and they share some clinical and biological features. 11,[27][28][29][30][31] The aberrant stem and progenitor cell populations have some cellular features in common with normal HSCs, including sustained self-renewal and proliferation capacity.…”

Section: Discussionmentioning

confidence: 99%

A 4-gene leukemic stem cell score can independently predict the prognosis of myelodysplastic syndrome patients

Wang

Lin

Yao³

et al. 2020

Blood Advances

Self Cite

View full text Add to dashboard Cite

Myelodysplastic syndrome (MDS) comprised a heterogeneous group of diseases. The prognosis of patients varies even in the same risk groups. Searching for novel prognostic markers is warranted. Leukemic stem cells (LSCs) are responsible for chemoresistance and relapse in leukemia. Recently, expressions of 17 genes related to stemness of LSCs were found to be associated with prognosis in acute myeloid leukemia patients. However, the clinical impact of LSC genes expressions in MDS, a disorder arising from hematopoietic stem cells, remains unclear. We analyzed expression profile of the 17 stemness-related genes in primary MDS patients and identified expression of 4 genes (LAPTM4B, NGFRAP1, EMP1, and CPXM1) were significantly correlated with overall survival (OS). We constructed an LSC4 scoring system based on the weighted sums of the expression of 4 genes and explored its clinical implications in MDS patients. Higher LSC4 scores were associated with higher revised International Prognostic Scoring System (IPSS-R) scores, complex cytogenetics, and mutations in RUNX1, ASXL1, and TP53. High-score patients had significantly shorter OS and leukemia-free survival (LFS), which was also confirmed in 2 independent validation cohorts. Subgroup analysis revealed the prognostic significance of LSC4 scores for OS remained valid across IPSS-R lower- and higher-risk groups. Furthermore, higher LSC4 score was an independent adverse risk factor for OS and LFS in multivariate analysis. In summary, LSC4 score can independently predict prognosis in MDS patients irrespective of IPSS-R risks and may be used to guide the treatment of MDS patients, especially lower-risk group in whom usually only supportive treatment is given.

show abstract

Section: Discussionmentioning

confidence: 99%

A 4-gene leukemic stem cell score can independently predict the prognosis of myelodysplastic syndrome patients

Wang

Lin

Yao³

et al. 2020

Blood Advances

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition, a study indicated that ABC transporters could be regulated by some member of the hedgehog (Hh) signaling pathway, therefore suggested this pathway might be a target to overcome MDR and increase chemotherapeutic response (23). In another studies, it was found that the expression of ABCB1, ABCC1 and ABCG2 genes was significantly higher in samples with higher Homeodomain-only protein homeobox (HOPX) gene expression (24), thus hypothesized there existed some interaction between HOPX and ABC on some pathway (25). Although our understanding of these mechanisms are limited, novel strategies are now available to allow for larger screening.…”

Section: Discussionmentioning

confidence: 99%

Co-expression of ATP binding cassette transporters is associated with poor prognosis in acute myeloid leukemia

Liu

Gong

et al. 2018

Oncol Lett

View full text Add to dashboard Cite

Abstract. Chemotherapy failure remains a challenge when treating patients with acute myeloid leukemia (AML), who often suffer from persistent or relapsed disease. The multidrug resistance (MDR) mediated by efflux transporters of the ATP binding cassette (ABC) superfamily is a major obstacle for successful chemotherapy. The present study aimed to elucidate whether the expression of ABC transporters was associated with prognostic factors and responses to chemotherapy in patients with AML, with particular focus on whether co-expression of multiple ABC transporters resulted in a worse prognosis. In the present study, the mRNA expression levels of ABC transporters ABCB1, ABCB4, ABCC1, ABCC4 and ABCG2 in bone marrow (BM) mononuclear cell (MNC) samples from 96 de novo patients with AML and in the peripheral blood (PB) MNC samples from 22 normal individuals were investigated using reverse transcription-quantitative polymerase chain reaction analysis. It was revealed that ABCB1, ABCC1, ABCC4 and ABCG2 were expressed at higher levels in patients with AML compared with normal individuals, whereas ABCB4 had a lower expression level. The expression of ABCB4 in patients with AML was significantly lower than in normal individuals (P<0.001). Patients risk status was associated with ABCB1 (P= 0.037), ABCC1 (P= 0.047), ABCC4 (P=0.015) and ABCG2 (P=0.027). The 4 genes were expressed a significantly higher levels in the poor response group compared with the good response group (ABCB1, P= 0.014; ABCC1, P= 0.021; ABCC4, P= 0.005; ABCG2, P= 0.009). The overexpression of the 4 ABC transporters and the complete remission rate were inversely correlated (P<0.001). These results suggest that the co-expression of multiple ABC transporters may contribute to a worse prognosis in AML.

show abstract

“…A consistent pattern of downregulation of HOPX-β mRNA expression coupled with HOPX-β promoter methylation levels in cancer cell lines and in various malign tissue types such us esophageal, colorectal, pancreatic in uterine and breast cancers have been previously described ( 8 , 10 , 11 , 12 , 13 , 15 , 18 ). On the other hand, in acute myeloid leukemia high HOPX expression was an unfavorable prognostic factor associated with low complete remission rate and short survival ( 30 ) and in sarcoma cells it was associated to metastases and its knockdown decreased metastatic activity ( 31 ). In this study, we interrogated the expression and methylation status and their clinical relevance in DTC.…”

Section: Discussionmentioning

confidence: 99%

HOPX homeobox methylation in differentiated thyroid cancer and its clinical relevance

Lima

Rubio

Silva

et al. 2018

Endocrine Connections

View full text Add to dashboard Cite

BackgroundThe inactivation of the tumor-suppressor homeodomain-only protein X (HOPX) usually involves promoter methylation in several cancer types. This study aimed to investigate the HOPX-β mRNA expression and promoter methylation and their clinical relevance in differentiated thyroid cancer (DTC).Patients and methodsClinicopathological data and paraffin-embedded thyroid tumor tissues from 21 patients with DTC and 6 with benign tumors (T) and their non-tumor parenchyma (NT) were investigated. Tumor cell lines (FTC238, FTC236 and WRO) were treated with demethylating agent. HOPX-β mRNA expression was assessed by qRT-PCR and methylation status by Q-MSP. Thyroid cancer data from Cancer Genome Atlas (TCGA) was also collected.ResultsHOPX-β mRNA re-expression in two cell lines treated with demethylating agent was observed concomitantly with reduced promoter methylation. Reduced mRNA expression in T group compared to their NT was observed, and reduced protein expression in T compared to NT was observed in three cases. Low mRNA expression with high methylation status was detected in 6/14 DTC samples. High methylation status was associated with older age at diagnosis, recurrent or progressive disease and with the presence of new neoplasm event post initial therapy while hyper-methylation correlated with worse overall survival, worse disease-free status and older age.ConclusionA moderate coupling of downregulation of HOPX-β mRNA expression in DTC followed by high HOPX-β promoter methylation was observed however; high HOPX promoter methylation status was associated with the worse prognosis of DTC patients.

show abstract

Higher HOPX expression is associated with distinct clinical and biological features and predicts poor prognosis in de novo acute myeloid leukemia

Cited by 38 publications

References 44 publications

A 4-gene leukemic stem cell score can independently predict the prognosis of myelodysplastic syndrome patients

A 4-gene leukemic stem cell score can independently predict the prognosis of myelodysplastic syndrome patients

Co-expression of ATP binding cassette transporters is associated with poor prognosis in acute myeloid leukemia

HOPX homeobox methylation in differentiated thyroid cancer and its clinical relevance

Contact Info

Product

Resources

About