Retraction: The lnc-SNHG1 Gene Is Overexpressed and Correlates with Increased White Blood Cell Count, Poor Induction Treatment Response, and Poor Survival Profile in Adult Acute Myeloid Leukemia

Objective: Long noncoding RNA small nucleolar RNA host gene 1 (lnc-SNHG1) is involved in leukemogenesis via mediating multiple pathways. The current study aimed to further explore its clinical roles in disease risk, clinical features, and prognosis in patients with acute myeloid leukemia (AML). Materials and Methods: A total of 161 adult AML patients, 50 patients as a disease control (DC) group, and 50 healthy individuals as a healthy control (HC) group were enrolled and bone marrow mononuclear cells were collected. Subsequently, reverse transcriptionquantitative polymerase chain reaction (RT-qPCR) was performed to measure lnc-SNHG1 expression. Results: Lnc-SNHG1 expression was higher in AML patients than in the DC and HC groups (both p<0.001), with good value in distinguishing AML patients from DC and HC individuals (area under the curve of 0.726 and 0.884, respectively). Moreover, lnc-SNHG1 expression was positively associated with white blood cell (WBC) count (p=0.008) but was not correlated with other clinical features such as cytogenetics, molecular genetics, and risk stratification (all p>0.05). Lnc-SNHG1 expression was also associated with a lower complete remission (CR) rate (p=0.001). Patients with lnc-SNHG1 expression in the fourth quantile had the worst CR rates compared to patients with lnc-SNHG1 expressions in the first, second, and third quantiles (all p<0.05). Furthermore, lnc-SNHG1 expression was correlated with unsatisfactory event-free survival (p<0.001) and overall survival (p=0.002), which were worst in patients with lnc-SNHG1 expression in the fourth quantile compared to patients with lnc-SNHG1 expressions in the first, second, and third quantiles (all p<0.05). Conclusion: Lnc-SNHG1 overexpression is associated with elevated WBC count, poor induction treatment response, and poor survival profile in cases of AML and it may serve as a potential indicator for AML.

Correlation analysis of long non-coding RNA TUG1 with disease risk, clinical characteristics, treatment response, and survival profiles of adult Ph- Acute lymphoblastic leukemia.

BACKGROUND: Long non-coding RNA taurine-upregulated gene 1 (lncRNA TUG1) is reported to be involved in the progression and development of several malignancies; however, its role in Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph- ALL) is unknown. The present study aimed to explore the correlation of lncRNA TUG1 with disease risk, disease condition, and prognosis of adult Ph- ALL. METHODS: Total 101 adult Ph- ALL patients and 40 bone marrow (BM) donors were included, followed by detection of BM monocyte cell lncRNA TUG1 expression by reverse transcription-quantitative polymerase chain reaction. According to the quantiles of lncRNA TUG1 expression in Ph- ALL patients, these patients were divided into four tiers: tier 1 (ranked in 0%~25%), tier 2 (ranked in 25%~50%), tier 3 (ranked in 50%~75%), and tier 4 (ranked in 75%~100%). RESULTS: LncRNA TUG1 was upregulated in Ph- ALL patients compared with healthy donors. Further analysis indicated that in Ph- ALL patients, higher lncRNA TUG1 tier was correlated with the presence of central nervous system leukemia, increased white blood cell level, and bone marrow blasts. Furthermore, higher lncRNA TUG1 tier was negatively associated with complete remission (CR) within 4 weeks, total CR, and allogeneic hematopoietic stem cell transplant achievement. In addition, higher lncRNA TUG1 tier was associated with decreased disease-free survival and overall survival, which was further verified to be an independent factor by Cox's regression analysis. CONCLUSION: lncRNA TUG1 presents potential to be a novel biomarker for disease risk assessment and survival surveillance in Ph- ALL management.

The FLT3-ITD mutation and the expression of its downstream signaling intermediates STAT5 and Pim-1 are positively correlated with CXCR4 expression in patients with acute myeloid leukemia.

Chemokine ligand 12(CXCL12) mediates signaling through chemokine receptor 4(CXCR4), which is essential for the homing and maintenance of Hematopoietic stem cells (HSCs) in the bone marrow. FLT3-ITD mutations enhance cell migration toward CXCL12, providing a drug resistance mechanism underlying the poor effects of FLT3-ITD antagonists. However, the mechanism by which FLT3-ITD mutations regulate the CXCL12/CXCR4 axis remains unclear. We analyzed the relationship between CXCR4 expression and the FLT3-ITD mutation in 466 patients with de novo AML to clarify the effect of FLT3-ITD mutations on CXCR4 expression in patients with AML. Our results indicated a positive correlation between the FLT3-ITD mutant-type allelic ratio (FLT3-ITD MR) and the relative fluorescence intensity (RFI) of CXCR4 expression in patients with AML (r = 0.588, P ≤ 0.0001). Moreover, the levels of phospho(p)-STAT5, Pim-1 and CXCR4 proteins were positively correlated with the FLT3-ITD MR, and the mRNA levels of CXCR4 and Pim-1 which has been revealed as one of the first known target genes of STAT5, were upregulated with an increasing FLT3-ITD MR(P < 0.05). Therefore, FLT3-ITD mutations upregulate the expression of CXCR4 in patients with AML, and the downstream signaling intermediates STAT5 and Pim-1 are also involved in this phenomenon and subsequently contribute to chemotherapy resistance and disease relapse in patients with AML. However, the mechanism must be confirmed in further experiments. The combination of CXCR4 antagonists and FLT3 inhibitors may improve the sensitivity of AML cells to chemotherapy and overcome drug resistance.

Relationship between CXC chemokine receptor 4 expression and prognostic significance in acute myeloid leukemia.

CXC chemokine receptor 4 (CXCR4) expression on acute myeloid leukemia (AML) cells correlated with stromal cell derived factor-1α (SDF-1α) and retained hematopoietic progenitors and leukemia cells within the bone marrow microenvironment. Here, we examined CXCR4 expression in 134 de novo AML and 21 controls by flow cytometry, evaluated the relationship between CXCR4 expression and clinical characteristics, and elucidated the prognostic significance of CXCR4 expression in AML prospectively. We found that the CXCR4 expression was significantly higher in AML patients than controls (P = .000). One hundred thirty four cases of de novo AML patients were divided into 2 groups according to the median of CXCR4 relative fluorescence intensity (RFI). CXCR4 high group (RFI >4.23) had markedly shorter overall survival (OS) and disease-free survival (DFS) than CXCR4 low group (RFI ≤4.23) in 106 AML patients who received chemotherapy (P = .002; .026, respectively). Furthermore, in the 87 non-M3 patients who received induction therapy, there was a significant decrease for OS but not for DFS in the CXCR4 high group (P = .047 and .178, respectively). Moreover, high levels of CXCR4 expression independently increased the risk of relapse in both all AML and non-M3 patients who achieved complete remission (CR) after chemotherapy (odds ratio = 1.090, P = .010; odds ratio = 1.068, P = .048, respectively). Collectively, our data suggest that CXCR4 overexpression was an independent prognostic factor for disease relapse and poorer OS in both all AML and non-M3 patients. CXCR4 expression levels can be determined at disease presentation by the flow rapidly and easily. As such, CXCR4 could be used as a potential therapeutic target in AML patients with poor prognosis.