title: Low expression of ASH2L protein correlates with a favorable outcome in acute myeloid leukemia.
abstract: ASH2L encodes a trithorax group protein that is a core component of all characterized mammalian histone H3K4 methyltransferase complexes, including mixed lineage leukemia (MLL) complexes. ASH2L protein levels in primary leukemia patient samples have not yet been defined. We analyzed ASH2L protein expression in 511 primary AML patient samples using reverse phase protein array (RPPA) technology. We discovered that ASH2L expression is significantly increased in a subset of patients carrying fms-related tyrosine kinase 3 (FLT3) mutations. Furthermore, we observed that low levels of ASH2L are associated with increased overall survival. We also compared ASH2L levels to the expression of 230 proteins previously analyzed on this array. ASH2L expression was inversely correlated with 32 proteins, mostly involved in cell adhesion and cell cycle inhibition, while a positive correlation was observed for 50 proteins, many of which promote cell proliferation. Together, these results indicate that a lower level of ASH2L protein is beneficial to AML patients.
authors.affiliation: a Department of Epigenetics and Molecular Carcinogenesis , The University of Texas MD Anderson Cancer Center , Science Park , Smithville , TX , USA.|b Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center , Houston , TX , USA.
authors.forename: Jill S
authors.initials: JS
authors.lastname: Butler
authors.affiliation: c Division of Molecular Hematology, Department of Leukemia , The University of Texas MD Anderson Cancer Center , Houston , TX , USA.
authors.forename: Yi Hua
authors.initials: YH
authors.lastname: Qiu
authors.affiliation: d Life Technologies Corporation , Carlsbad , CA , USA.
authors.forename: Nianxiang
authors.initials: N
authors.lastname: Zhang
authors.affiliation: e Department of Bioinformatics and Computational Biology , The University of Texas MD Anderson Cancer Center , Houston , TX , USA.
authors.forename: Suk-Young
authors.initials: SY
authors.lastname: Yoo
authors.affiliation: f Department of Biomedical Informatics , The Ohio State University College of Medicine , Columbus , OH , USA.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Coombes
authors.affiliation: a Department of Epigenetics and Molecular Carcinogenesis , The University of Texas MD Anderson Cancer Center , Science Park , Smithville , TX , USA.|b Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center , Houston , TX , USA.
authors.forename: Sharon Y R
authors.initials: SY
authors.lastname: Dent
authors.affiliation: c Division of Molecular Hematology, Department of Leukemia , The University of Texas MD Anderson Cancer Center , Houston , TX , USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Kornblau
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006657:Histones / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008745:Methylation; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D000090243:Nucleophosmin; D011379:Prognosis; D011499:Protein Processing, Post-Translational; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: C485622:ASH2L protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D006657:Histones; D009687:Nuclear Proteins; D014157:Transcription Factors; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3
keywords: ASH2L; chromatin; epigenetics; histone modifications; leukemia; methyltransferase