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

Genetic heterogeneity is the basis of clinical heterogeneity among different subtypes of AML. We have successfully cloned a gene related to AML termed from a FAB-M2 patient's sample of a second largest AML pedigree. Then we revealed at least three splice variants, named as , and , and found miR...

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Published in:Oncotarget 2017-11, Vol.8 (60), p.101372-101382
Main Authors: Huang, Yuan-Mao, Zheng, Yi, Li, Jing-Gang, Wang, Xue-Chun, Wang, Ze-Chuan, Chen, Wan-Ling, Pan, Li-Li, Li, Yang, Luo, Dong-Feng, Wang, Shao-Yuan
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Language:English
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Summary:Genetic heterogeneity is the basis of clinical heterogeneity among different subtypes of AML. We have successfully cloned a gene related to AML termed from a FAB-M2 patient's sample of a second largest AML pedigree. Then we revealed at least three splice variants, named as , and , 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 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 gene might increase FAB-M2 susceptibility in Han population and act as a useful candidate biomarker for FAB-M2 screening. We also demonstrated that 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 as a potential pathogenic gene for FAB-M2.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.21276