Yongji Wu

Expression of tumor-associated macrophages and vascular endothelial growth factor correlates with poor prognosis of peripheral T-cell lymphoma, not otherwise specified.

To elucidate the expression of tumor-associated macrophages (TAMs) and vascular endothelial growth factor (VEGF) in peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), and their correlation with patient clinical characteristics and overall survival (OS), immunohistochemistry stains for CD68 and VEGF were applied to 38 tissue specimens of PTCL-NOS. The CD68+ cell content and VEGF-positive rates were significantly higher in PTCL-NOS tissues (p < 0.05). TAMs were significantly related to bone marrow invasion, international prognostic index (IPI) score, and response to treatment (p < 0.05). The 2-year OS of the high-TAMs-expression group (>50/hpf) was 22.2%, and that of the low-TAMs-expression group (<50/hpf) was 52.8% (p < 0.05). The expression of VEGF was closely related to tumor staging, bone marrow invasion, and IPI score (p < 0.05). The 2-year OS of the VEGF-positive group was 25.4%, and that of the VEGF-negative group was 83.3% (p < 0.01). Therefore, TAMs and VEGF, which were significantly correlated to prognosis of the disease, may be involved in the tumorigenesis, progression, invasion, and angiogenesis of PTCL-NOS.

Overexpression of the novel oncogene SALL4 and activation of the Wnt/β-catenin pathway in myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are a group of heterogeneous clonal stem cell diseases with a tendency to progress to leukemic transformation. The cytogenetic and molecular pathogenesis of MDS has not been well understood. SALL4, a newly identified oncogene, modulates stem cell pluripotency and self-renewal capability in embryonic development and also plays a role in leukemogenesis. Overexpression of SALL4 induces MDS-like features and subsequent leukemic progression in transgenic mice. Here, we examined SALL4 expression levels in bone marrow mononuclear cells from MDS patients, acute myeloid leukemia (AML) patients, and normal control subjects using a semiquantitative reverse transcription polymerase chain reaction. Higher levels of SALL4 expression were seen in MDS and AML samples than in control samples. The expression level of SALL4 positively correlated with those of MYC and CCND1, both of which are downstream target genes in the Wnt/beta-catenin pathway. We therefore propose that SALL4 plays a critical role in the pathogenesis of MDS by causing the aberrant activation of the Wnt/beta-catenin pathway.

Telomerase gene mutation screening and telomere overhang detection in Chinese patients with acute myeloid leukemia.

Abstract Loss-of-function mutations in telomerase complex genes reduce telomerase activity, and can clinically manifest as bone marrow failure disease, which predisposes to acute myeloid leukemia (AML). Telomerase dysfunction also leads to short telomeric overhang, which is a crucial telomeric structural component, and potentially results in chromosome instability. We screened variants in telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC) genes, and investigated the 3’-overhang length in bone marrow samples from 72 Chinese patients with AML (61 de novo, 11 secondary, excluding M3), aged 13–77. Cytogenetics, disease severity and short-term survival were evaluated. Three TERT mutations (n896G>A, n1079C>G and n1451G>C) were identified. Mutation carriers had short overhangs and a poor prognosis. We found that overhang lengths were much shorter in AML compared to normal controls (p < 0.001). Short overhangs were related to a high percentage of karyotype abnormalities and poor prognosis (73.8% in short overhang group vs. 30% in normal group, p=0.001). Multivariant analysis showed that overhang length, age and unfavorable chromosome abnormalities served as independent prognostic markers in AML (Cox regression, p=0.001). These data raise the possibility that short overhang length may predict poor prognosis in patients with AML. These findings would have to be confirmed in large, prospective studies.

Telomerase gene screening and telomere overhang detection in Chinese patients with myelodysplastic syndrome

BACKGROUND Telomerase disfunction leads to short telometric overhangs, potentially resulting in chromosome instability. AIMS To better understand the role of overhang length in the progression of myelodysplastic syndrome (MDS). METHODS Bone marrow samples of 62 Chinese MDS patients were screened for TERT and TERC gene variants. Overhangs length was investigated. RESULTS No mutation was identified. MDS patients had shorter overhangs compared to controls. Abnormal karyotype ones had shorter overhang compared to normal. Telomeric overhang length decreased as IPSS/WPSS value increased. CONCLUSIONS Overhang changes in accordance with IPSS/WPSS in MDS. Short overhang may be an independent factor for poor prognosis in MDS.