A case of Ph acute lymphoblastic leukemia and EGFR mutant lung adenocarcinoma synchronous overlap: may one TKI drug solve two diseases?

Background: Philadelphia chromosome positive (Ph) acute lymphoblastic leukemia (ALL) refers to ALL patients with t(9;22) cytogenetic abnormalities, accounting for about 25% of ALL. Lung adenocarcinoma (LUAD) is the most common pathological type of non-small-cell lung cancer, which has a frequency of approximately 45% cases with mutations in EGFR. Both Ph ALL and EGFR mutant LUAD are involved in the pathogenesis of the abnormal activation of the tyrosine kinase pathway.

SLIT2 promoter hypermethylation predicts disease progression in chronic myeloid leukemia.

Background: Aberrant DNA methylation plays a crucial role in the progression of myeloid neoplasms. Previously, our literature reported that slit guidance ligand 2 (SLIT2) promoter methylation was associated with disease progression and indicated a poor prognosis in patients with myelodysplastic syndrome. Herein, we further investigated the clinical implications and role of SLIT2 promoter methylation in patients with chronic myeloid leukemia (CML).

SLIT2 promoter hypermethylation-mediated SLIT2-IT1/miR-218 repression drives leukemogenesis and predicts adverse prognosis in myelodysplastic neoplasm.

Epigenetic modifications have been found to play crucial roles in myelodysplastic neoplasm (MDS) progression. Previously, we investigated genome-wide DNA methylation alterations during MDS evolution to acute myeloid leukemia (AML) by next-generation sequencing (NGS). Herein, we further determined the role and clinical implications of an evident methylation change in CpG islands at the SLIT2 promoter identified by NGS.

DNA methylation-mediated differential expression of DLX4 isoforms has opposing roles in leukemogenesis.

Background: Previously, we reported the expression of DLX4 isoforms (BP1 and DLX7) in myeloid leukemia, but the functional role of DLX4 isoforms remains poorly understood. In the work described herein, we further determined the underlying role of DLX4 isoforms in chronic myeloid leukemia (CML) leukemogenesis.

Methods: The expression and methylation of DLX4 isoforms were detected by real-time quantitative PCR (RT-qPCR) and real-time quantitative methylation-specific PCR (RT-qMSP) in patients with CML.

Reduced expression of lncRNA DLEU7-AS1 is a novel favorable prognostic factor in acute myeloid leukemia.

The objective of our study was to measure DLEU7-AS1 expression in de novo acute myeloid leukemia (AML) whilst also analyzing its clinical relevance. We used gene expression data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Cancer Cell Line Encyclopedia (CCLE) and Genotype-Tissue Expression project (GTEx) to assess the expression profile of DLEU7-AS1 in pan-cancers, cancer cell lines and normal tissues. Reverse transcription-quantitative PCR was used to measure DLEU7-AS1 expression in bone marrow from 30 normal individuals and 110 patients with de novo AML.

Comprehensive analysis of SPAG1 expression as a prognostic and predictive biomarker in acute myeloid leukemia by integrative bioinformatics and clinical validation.

Background: Recently, an increasing number of studies have reported that sperm-associated antigen (SPAG) proteins play crucial roles in solid tumorigenesis, and may serve as potentially helpful biomarkers for cancer diagnosis and prognosis. However, very few studies systematically investigated the expression of SPAG family members and their clinical significance in acute myeloid leukemia (AML).

Methods: The expression of SPAGs and their prognostic significance in AML were determined by a systematic analysis on data gathered from public databases, and the results were validated in clinical samples.

Distinct associations of NEDD4L expression with genetic abnormalities and prognosis in acute myeloid leukemia.

Background: There is mounting evidence that demonstrated the association of aberrant NEDD4L expression with diverse human cancers. However, the expression pattern and clinical implication of NEDD4L in acute myeloid leukemia (AML) remains poorly defined.

Methods: We systemically determined NEDD4L expression with its clinical significance in AML by both public data and our research cohort.

[Overexpression of LncRNA ITGB2-AS1 Predicts Adverse Prognosis in Acute Myeloid Leukemia].

Objective: LncRNA ITGB2-AS1 has been found to play important roles in the occurrence and development of human solid tumors. However, its role in hematological diseases, especially acute myeloid leukemia (AML), remains unclear. The aim of this study was to identify the expression pattern of ITGB2-AS1 in AML patients and to further explore its clinical significance.

Abnormal expression and methylation of PRR34-AS1 are associated with adverse outcomes in acute myeloid leukemia.

It was previously reported that PRR34-AS1 was overexpressed in some solid tumors. PRR34-AS1 promoter was shown to have a differential methylation region (DMR), and was hypomethylated in acute myeloid leukemia (AML). Therefore, the present study used real-time quantitative PCR (RQ-PCR) to explore the expression characteristics of PRR34-AS1 in AML.

Identification and validation of obesity-related gene LEP methylation as a prognostic indicator in patients with acute myeloid leukemia.

Background: Obesity confers enhanced risk for multiple diseases including cancer. The DNA methylation alterations in obesity-related genes have been implicated in several human solid tumors. However, the underlying role and clinical implication of DNA methylation of obesity-related genes in acute myeloid leukemia (AML) has yet to be elucidated.

Genome-wide methylation sequencing identifies progression-related epigenetic drivers in myelodysplastic syndromes.

The potential mechanism of myelodysplastic syndromes (MDS) progressing to acute myeloid leukemia (AML) remains poorly elucidated. It has been proved that epigenetic alterations play crucial roles in the pathogenesis of cancer progression including MDS. However, fewer studies explored the whole-genome methylation alterations during MDS progression.

Methylation-independent expression is a potential biomarker affecting prognosis in cytogenetically normal acute myeloid leukemia.

Abnormal expression of has been identified in numerous solid tumors. However, expression and its regulation are little known in acute myeloid leukemia (AML). The purpose of this study was to evaluate the expression and regulation of and the clinical implications of aberration in AML.

Expression and prognosis analysis of family in acute myeloid leukemia.

DNA methyltransferases () by regulating DNA methylation play crucial roles in the progression of hematologic malignancies, especially for acute myeloid leukemia (AML). Accumulating investigations have identified the high incidence of mutation in AML, and it is correlated with poor prognosis. Although a few studies have shown the expression of and their clinical significance in AML, the results remain to be discussed.

Identification and validation of prognosis-related DLX5 methylation as an epigenetic driver in myeloid neoplasms.

The deregulated DLX gene family members DLX1/2/3/4/5/6 (DLXs) caused by DNA methylation has been demonstrated in various cancers with therapeutic target value. However, the potential role of DLXs methylation in myeloid neoplasms such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) remains to be elucidated. Clinical significance of DLXs methylation/expression was analyzed in patient with AML and MDS.

Hypomethylation of MIR-378 5'-flanking region predicts poor survival in young patients with myelodysplastic syndrome.

Background: Previous studies have disclosed up-regulation of MIR-378 in acute myeloid leukemia (AML), and might consequently affect the outcome of the patients. Correspondingly, hypomethylation of MIR-378 was also identified in AML, particularly for FAB-M2 subtype with t(8;21) chromosomal translocation. Nevertheless, the methylation status of MIR-378 has not been illustrated in myelodysplastic syndrome (MDS).

EZH2 dysregulation: Potential biomarkers predicting prognosis and guiding treatment choice in acute myeloid leukaemia.

Accumulating studies have proved EZH2 dysregulation mediated by mutation and expression in diverse human cancers including AML. However, the expression pattern of EZH2 remains controversial in acute myeloid leukaemia (AML). EZH1/2 expression and mutation were analysed in 200 patients with AML.

DOK6 promoter methylation serves as a potential biomarker affecting prognosis in de novo acute myeloid leukemia.

Background: Downstream of tyrosine kinase 6 (DOK6), which is specifically expressed in the nervous system, was previously recognized as an adapter only in neurite outgrowth. Recent studies also demonstrated the potential role of DOK6 in solid tumors such as gastric cancer and breast cancer. However, previous studies of DOK6 have not dealt with its roles in myeloid malignancies.

methylation correlates with disease progression in patients with chronic myeloid leukemia.

Background: Our previous study has reported that aberrant methylation was associated with poor prognosis in AML, and it correlated with disease progression in MDS. Herein, we further determined methylation and its clinical significance in the other myeloid malignance - chronic myeloid leukemia (CML).

Methods: methylation was examined by real-time quantitative methylation-specific PCR and bisulfite sequencing PCR, whereas expression was detected by real-time quantitative PCR.

Down-regulation of miR-29c is a prognostic biomarker in acute myeloid leukemia and can reduce the sensitivity of leukemic cells to decitabine.

Background: MicroRNA-29c (miR-29c) is abnormally expressed in several cancers and serves as an important predictor of tumor prognosis. Herein, we investigate the effects of abnormal miR-29c expression and analyze its clinical significance in acute myeloid leukemia (AML) patients. In addition, decitabine (DAC) has made great progress in the treatment of AML in recent years, but DAC resistance is still common phenomenon and the mechanism of resistance is still unclear.

Promoter methylation of the candidate tumor suppressor gene TCF21 in myelodysplastic syndrome and acute myeloid leukemia.

Transcription factor 21 () has been identified as a candidate tumor suppressor gene which was epigenetically inactivated in a variety of human cancers. However, methylation pattern remains unknown in hematologic malignancies. The aim of this study was to investigate methylation and its clinical relevance in myelodysplastic syndrome (MDS) and non-M3 acute myeloid leukemia (AML).

BCL2 overexpression: clinical implication and biological insights in acute myeloid leukemia.

Background: BCL2 protein inhibitor venetoclax (ABT-199) has been authorized by Food and Drug Administration for relapsed/refractory chronic lymphoid leukemia with 17p deletion. Although venetoclax/ABT-199 also caused cell death in acute myeloid leukemia (AML), whether it could be applied to clinical treatment needs further studies. Here, we revealed clinical implication of BCL2 overexpression in de novo adult AML, and may provide theoretical basis for targeted therapy using venetoclax.

/ dysregulation predicts clinical outcome and facilitates leukemogenesis by activating PI3K/Akt signaling pathway in acute myeloid leukemia.

() has been reported as a significant cancer-associated microRNA, which was often epigenetically silenced and acted as a tumor suppressor gene in diverse human solid tumors. Conversely, recent studies show that overexpression was identified in both adult and pediatric acute myeloid leukemia (AML), suggesting that it might play an oncogenic role of in AML. However, the role of during leukemogenesis remains to be elucidated.