title: [Clinical significance of common leukemia gene mutations in patients with acute promyelocytic leukemia].
abstract: This study was aimed to explore whether multiple common gene mutations of leukemia synergistically involved in acute promyelocytic leukemia (APL) pathogenesis, and to investigate their relevance to clinical features, cytogenetics and molecular risk stratification. 84 specimens of admitted de novo APL patients from February 2005 to October 2010 were collected, the gene mutations of bone marrow mononuclear cells and clinical features of mutation-positive patients were analyzed by genomic DNA-PCR. The results indicated that the prevalence of mutations was 60.7% (51/84), in which the mutations with the highest incidence were found as FLT3-ITD, reaching 27.4% (23/84). Next, there were 12 cases WT1 mutation, 9 for FLT3-TKD, 7 for TET2, 5 for N-RAS, 4 for ASXL1, 2 for EZH2 mutation and 1 positive case in MLL-PTD, IDH1 and CBL mutation respectively. No mutation was found in other JAK1, DNMT3, c-Kit, NPM1, IDH2, RUNX1 and JAK2 (V617F) common leukemia-related genes. Combined analysis with clinical data demonstrated that the patients with FLT3-ITD mutation displayed higher white blood cell counts, while the patients with N-RAS mutation showed lower platelet counts. Overall survival of these patients was obviously shorten as compared with patients with wild-type. This difference between mutant and wild-type of all above mentioned cases was statistically significant (P < 0.05). The difference between APL with simple t (15;17) and additional abnormal karyotype was not statistically significant. It is concluded that the FLT3-ITD mutation is recurrent genetic change in APL, and together with N-RAS mutation indicates poor prognosis. Additional abnormal karyotype does not associate with prognosis of APL.
authors.affiliation: Jiangsu Institute of Hematology, Jiangsu Province, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Yin
authors.forename: Ai-Ning
authors.initials: AN
authors.lastname: Sun
authors.forename: Xiao-Peng
authors.initials: XP
authors.lastname: Tian
authors.forename: Hong
authors.initials: H
authors.lastname: Tian
authors.forename: Rong-Xian
authors.initials: RX
authors.lastname: Wang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yang
authors.forename: Xiu-Li
authors.initials: XL
authors.lastname: Wang
authors.forename: De-Pei
authors.initials: DP
authors.lastname: Wu
authors.forename: Hui-Ying
authors.initials: HY
authors.lastname: Qiu
authors.forename: Jin-Lan
authors.initials: JL
authors.lastname: Pan
authors.forename: Jian-Nong
authors.initials: JN
authors.lastname: Cen
authors.forename: Jian-Ying
authors.initials: JY
authors.lastname: Liang
authors.forename: Su-Ning
authors.initials: SN
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D049308:Dioxygenases; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D011905:Genes, ras; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D063151:Polycomb Repressive Complex 2 / Q000235:genetics; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D020080:Tandem Repeat Sequences; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: C473949:ASXL1 protein, human; D004268:DNA-Binding Proteins; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D000090243:Nucleophosmin; D049308:Dioxygenases; C541081:TET2 protein, human; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; C497970:FLT3 protein, human; D019009:Proto-Oncogene Proteins c-kit; D051941:fms-Like Tyrosine Kinase 3