We investigated the correlation between FLT3 expression and IL10 gene promoter polymorphism in acute myeloid leukemia with RUNX1-RUNX1T1 and their clinical significance. FLT3 mRNA expression was measured by real-time quantitative PCR (qPCR) and immunohistochemical staining (IHC) on bone marrow (BM) leukemic cells. IL10 gene promoter polymorphisms including rs1800896 (G-1082A), rs1800871 (C-819T), and rs1800872 (C-592T) were genotyped by direct sequencing. Among 45 enrolled patients, 32 (71.1 %) exhibited FLT3 overexpression, whose FLT3 mRNA level was higher than normal cut-off value (0.02). The IHC results also consisted with FLT3 mRNA expression data achieved by qPCR. The FLT3 mRNA level was significantly different among 3 IHC staining groups (P < 0.0001); 0.031 ± 0.041, 0.106 ± 0.097 and 0.588 ± 0.573 in IHC negative, intermediate and positive group, respectively. Interestingly, the FLT3 expression level was correlated with the percentage of BM CD34 positive cells (R = 0.360, P = 0.016). The elevated FLT3 expression at initial BM were decreased after remission and maintained lower than the cut-off level. FLT3 expression was not dependent on IL10 gene promoter polymorphisms. FLT3 overexpression itself did not demonstrate significant effects on overall survival (OS). However, it is notable that IL10 rs1800896 GA genotype tended to have a lower estimated mean OS (20.1 months) compared to GG genotype (54.6 months), but the statistical significance was not derived because of limited number of patients in this study (P = 0.072). Further studies including more type of leukemia and patients may be helpful to understand the relations between cytokine genotype and FLT3 expression and their prognostic impact.
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http://dx.doi.org/10.1007/s11033-014-3786-1 | DOI Listing |
Biomolecules
January 2025
Department of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, AB T6G 1R1, Canada.
Small interfering RNA (siRNA) therapy in acute myeloid leukemia (AML) is a promising strategy as the siRNA molecule can specifically target proteins involved in abnormal cell proliferation. The development of a clinically applicable method for delivering siRNA molecules is imperative due to the challenges involved in effectively delivering the siRNA into cells. We investigated the delivery of siRNA to AML MOLM-13 cells with the use of two lipid-substituted polyethyleneimines (PEIs), a commercially available reagent (Prime-Fect) and a recently reported reagent with improved lipid substitution (PEI1.
View Article and Find Full Text PDFLeukemia
January 2025
Australian Centre for Blood Diseases (ACBD), School of Translational Medicine, Monash University, Melbourne, VIC, Australia.
Early T-cell Precursor Acute Lymphoblastic Leukemia (ETP-ALL) is an immature subtype of T-cell acute lymphoblastic leukemia (T-ALL) commonly show deregulation of the LMO2-LYL1 stem cell transcription factors, activating mutations of cytokine receptor signaling, and poor early response to intensive chemotherapy. Previously, studies of the Lmo2 transgenic mouse model of ETP-ALL identified a population of stem-like T-cell progenitors with long-term self-renewal capacity and intrinsic chemotherapy resistance linked to cellular quiescence. Here, analyses of Lmo2 transgenic mice, patient-derived xenografts, and single-cell RNA-sequencing data from primary ETP-ALL identified a rare subpopulation of leukemic stem cells expressing high levels of the cytokine receptor FLT3.
View Article and Find Full Text PDFLeukemia
January 2025
Department of Human Genetics, KU Leuven, Leuven, Belgium.
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological disease originating from the malignant transformation of T-cell progenitors, caused by the accumulation of genetic aberrations. One-fifth of T-ALL patients are characterized by ectopic expression of the homeobox transcription factor TLX3. However, the role of TLX3 in T-ALL remains elusive, partly due to the lack of suitable study models.
View Article and Find Full Text PDFLeuk Res Rep
December 2024
Independent Researcher, Gimpo-si, Gyeonggi-do 10090, South Korea.
Prognostication of acute myeloid leukemia (AML) at initial diagnosis relies on identification of pre-determined underlying genetic abnormalities. Nevertheless, the disease course of AML remains highly unpredictable and robust reliable prognostic biomarkers for newly diagnosed AML are lacking. We retrospectively explored two publicly available AML RNA-Seq datasets and found that inferior overall survival was associated with high- and low- transcript levels (" / ") compared to low- and high- transcript levels (" / ") in adult AML patients, with a hazard ratio for death of at least 2.
View Article and Find Full Text PDFSci Rep
January 2025
Department of General Surgery, Qilu Hospital, Shandong University, Jinan, 250012, Shandong Province, China.
The crosstalk between cancers and the immune microenvironment plays a critical role in malignant progression. FMS-like tyrosine kinase 3 (FLT3) is a frequently mutated gene in acute myeloid leukemia (AML). However, its role in solid cancers remains poorly understood.
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