title: HO-1, RET and PML as possible markers for risk stratification of acute myelocytic leukemia and prognostic evaluation.
abstract: Heme oxygenase-1 (HO-1) is an inducible isoform of HO that is activated in response to oxidative stress and has anti-apoptotic and pro-proliferative effects on leukemia cells. RET, a tyrosine kinase receptor; its expression levels are associated with the differentiation degree of acute myelocytic leukemia (AML) cells. The promyelocytic leukemia (PML) gene inhibits cell proliferation and tumor growth, participates in the differentiation of hematopoietic progenitor cells and induces cell apoptosis. However, the association between the expression levels of HO-1, RET and PML genes and the risk stratification of AML and prognosis have not previously been reported. In the present study, HO-1 was expressed in the human AML Kasumi-1, HL-60 and THP-1 cell lines, and HO-1 expression was regulated by Hemin (20 µmol/l) and ZnPPIX (10 µmol/l). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis demonstrated that expression of RET and PML were positively and negatively correlated with HO-1 expression, respectively. Bone marrow samples (18 favorable, 55 intermediate, 15 adverse and 2 unknown karyotype AML cases and 20 healthy donors) were collected from 90 randomly selected AML patients upon their first visit. The mRNA and protein expression of HO-1, RET and PML in samples was detected by RT-qPCR and western blot analysis. At the mRNA level, the adverse group expressed significantly higher levels of HO-1 and RET compared with the levels in the favorable and normal groups. The PML mRNA expression levels in adverse patient samples was lower compared with those of the intermediate group and favorable group. Western blot analysis demonstrated that the expression levels of HO-1, RET and PML proteins in all risk groups exhibited the same pattern of expression as was observed for the mRNA levels. The overall survival and relapse-free survival rates were shortest in AML patients with high HO-1 expression (Kaplan-Meier; log-rank, P<0.01). The results of the present study therefore indicate that HO-1, RET and PML may be critical in the risk-stratification and prognosis of AML. However, additional samples and clinical data should be collected and analyzed in order to provide stronger evidence for this hypothesis.
authors.affiliation: Clinical Medical College, Guiyang Medical University, Guiyang, Guizhou 550004, P.R. China.
authors.forename: Meisheng
authors.initials: M
authors.lastname: Yu
authors.affiliation: Guizhou Province Laboratory of Hematopoietic Stem Cell Transplantation Centre, Affiliated Hospital of Guiyang Medical University, Guiyang, Guizhou 550004, P.R. China ; Department of Hematology, Affiliated Hospital of Guiyang Medical University, Guiyang, Guizhou 550004, P.R. China.
authors.forename: Jishi
authors.initials: J
authors.lastname: Wang
authors.affiliation: Clinical Medical College, Guiyang Medical University, Guiyang, Guizhou 550004, P.R. China ; Department of Pharmacy, Guiyang Medical University, Guiyang, Guizhou 550004, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Ma
authors.affiliation: Clinical Medical College, Guiyang Medical University, Guiyang, Guizhou 550004, P.R. China.
authors.forename: Shuya
authors.initials: S
authors.lastname: Chen
authors.affiliation: Clinical Medical College, Guiyang Medical University, Guiyang, Guizhou 550004, P.R. China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Pharmacy, Affiliated Baiyun Hospital of Guiyang Medical University, Guiyang, Guizhou 550058, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Fang
authors.affiliation: Clinical Medical College, Guiyang Medical University, Guiyang, Guizhou 550004, P.R. China.
authors.forename: Nana
authors.initials: N
authors.lastname: Zhe
keywords: AML; HO-1; PML; RET; prognosis; risk stratification