Lentivirus-mediated RNA interference targetingFAMLF-1inhibits cell growth and enhances cell differentiation of acute myeloid leukemia partially differentiated cells via inhibition of AKT and c-MYC

Abstract

Genetic heterogeneity is the basis of clinical heterogeneity among different subtypes of AML. We have successfully cloned a gene related to AML termed FAMLF from a FAB-M2 patient's sample of a second largest AML pedigree. Then we revealed at least three splice variants, named as FAMLF-1, FAMLF-2 and FAMLF-3, and found miR181a1/b1 in the second intron of FAMLF gene family. Higher expression of FAMLF-1 was related to a higher complete remission (CR) rate, but shorter relapse free survival (RFS) in AML. We further found that the FAMLF-1 single nucleotide polymorphism (SNP) haplotype and its expression were positively correlated to clinical parameters of acute myeloid leukemia partially differentiated (FAB-M2) patients, but not FAB non-M2 patients or Acute Monocytic Leukemia (FAB-M5) patients. GTAGG SNP haplotype of FAMLF gene might increase FAB-M2 susceptibility in Han population and act as a useful candidate biomarker for FAB-M2 screening. We also demonstrated that FAMLF-1 gene silencing in FAB-M2 cells could lead to proliferation inhibition, cell cycle G0/G1 phase arrest, and differentiation promotion independent of its intronic miR-181a1, which might be related to Akt/c-Myc pathway. These findings reveal a role of FAMLF-1 as a potential pathogenic gene for FAB-M2.

Enzasataurin Enhances ATRA-induced Differentiation of Acute Myeloid Leukemia Cells

“…Akt can positively or negatively control differentiation of leukemia cells depending on cell type and differentiation inducer [31,46]. In HL-60 cells, Akt activation is required for ATRA-induced differentiation [29].…”

Platelet-derived growth factor-B signalling might promote epithelial-mesenchymal transition in gastric carcinoma cells through activation of the MAPK/ERK pathway

“…Briefly, 1 × 10 5 MKN28 and MKN45 cells were seeded in each well of a 6-well plate in 500 µl of complete media at 37°C in a 5% CO 2 incubator for 24 h, and then transduced by lentiviral vectors at a multiplicity of infection of 10 : 1 [ 16 ]. Transduction was carried out in the presence of Polybrene (8 µg/ml).…”

MiR-181b Inhibits the Proliferation of Lymphoma Rajixi Cell Line by Regulating the Expression of Target Gene FAMLF

“…Wang used real-time quantitative PCR to study the expression of FAMLF alternative splicing transcript consensus sequence (FAMLF-CS) in peripheral blood mononuclear cells (PBMC) of 119 acute leukemia (AL) patients and 104 healthy controls (17). And CD34 + cells from 12 AL patients and 10 healthy donors (18)(19)(20). The total expression of FAMLF was quantified using the 363 bp consensus sequence as the target (21)(22)(23).…”