Oncotarget

Research Papers:

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

Yuan-Mao Huang, Yi Zheng, Jing-Gang Li, Xue-Chun Wang, Ze-Chuan Wang, Wan-Ling Chen, Li-Li Pan, Yang Li, Dong-Feng Luo and Shao-Yuan Wang _

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Oncotarget. 2017; 8:101372-101382. https://doi.org/10.18632/oncotarget.21276

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Abstract

Yuan-Mao Huang1,2,3, Yi Zheng1, Jing-Gang Li2, Xue-Chun Wang1, Ze-Chuan Wang1, Wan-Ling Chen1, Li-Li Pan2, Yang Li2, Dong-Feng Luo1 and Shao-Yuan Wang1,2

1Union Clinical Medical College, Fujian Medical University, Fuzhou 350001, P.R. China

2Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, P.R. China

3Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou 363000, P.R. China

Correspondence to:

Shao-Yuan Wang, email: shaoyuanwang@mail.fjmu.edu.cn

Keywords: acute myeloid leukemia partially differentiated (FAB-M2), FAMLF-1 gene, miR-181a1, single nucleotide polymorphism haplotype, pathogenesis

Received: April 19, 2017     Accepted: September 03, 2017     Published: September 26, 2017

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.


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