title: A six gene expression signature defines aggressive subtypes and predicts outcome in childhood and adult acute lymphoblastic leukemia.
abstract: Abnormal gene expression in cancer represents an under-explored source of cancer markers and therapeutic targets. In order to identify gene expression signatures associated with survival in acute lymphoblastic leukemia (ALL), a strategy was designed to search for aberrant gene activity, which consists of applying several filters to transcriptomic datasets from two pediatric ALL studies. Six genes whose expression in leukemic blasts was associated with prognosis were identified:three genes predicting poor prognosis (AK022211, FASTKD1 and STARD4) and three genes associated with a favorable outcome (CAMSAP1, PCGF6 and SH3RF3). Combining the expression of these 6 genes could successfully predict prognosis not only in the two discovery pediatric ALL studies, but also in two independent validation cohorts of adult patients, one from a publicly available study and one consisting of 62 newly recruited Chinese patients. Moreover, our data demonstrate that our six gene based test is particularly efficient in stratifying MLL or BCR.ABL negative patients. Finally, common biological traits characterizing aggressive forms of ALL in both children and adults were found, including features of dormant hematopoietic stem cells, suggesting new therapeutic strategies.
authors.affiliation: State Key Laboratory for Medical Genomics and Department of Hematology, Shanghai Institute of Hematology, Collaborative Innovation Center of Systems Biomedicine, Pôle Sino-Français des Sciences du Vivant et Genomique, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|INSERM, Université Grenoble Alpes, Institut Albert Bonniot, Grenoble, France.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory for Medical Genomics and Department of Hematology, Shanghai Institute of Hematology, Collaborative Innovation Center of Systems Biomedicine, Pôle Sino-Français des Sciences du Vivant et Genomique, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: Mi
authors.affiliation: INSERM, Université Grenoble Alpes, Institut Albert Bonniot, Grenoble, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Debernardi
authors.affiliation: INSERM, Université Grenoble Alpes, Institut Albert Bonniot, Grenoble, France.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Vitte
authors.affiliation: INSERM, Université Grenoble Alpes, Institut Albert Bonniot, Grenoble, France.
authors.forename: Anouk
authors.initials: A
authors.lastname: Emadali
authors.affiliation: NYU Cancer Institute, NYU Langone Medical Center, New York, USA.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Meyer
authors.affiliation: Laboratoire Jean Kuntzmann, CNRS, Grenoble, France.
authors.forename: Konstantina
authors.initials: K
authors.lastname: Charmpi
authors.affiliation: Laboratoire Jean Kuntzmann, CNRS, Grenoble, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Ycart
authors.affiliation: INSERM, Université Grenoble Alpes, Institut Albert Bonniot, Grenoble, France.
authors.forename: Mary B
authors.initials: MB
authors.lastname: Callanan
authors.affiliation: NYU Cancer Institute, NYU Langone Medical Center, New York, USA.
authors.forename: William L
authors.initials: WL
authors.lastname: Carroll
authors.affiliation: INSERM, Université Grenoble Alpes, Institut Albert Bonniot, Grenoble, France.
authors.forename: Saadi
authors.initials: S
authors.lastname: Khochbin
authors.affiliation: INSERM, Université Grenoble Alpes, Institut Albert Bonniot, Grenoble, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Rousseaux
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D002648:Child; D002681:China; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000235:genetics; D063150:Polycomb Repressive Complex 1 / Q000235:genetics; D057285:Precision Medicine / Q000379:methods; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology*; D011446:Prospective Studies; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D059467:Transcriptome; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C000588920:CAMSAP1 protein, human; D026901:Membrane Transport Proteins; D008869:Microtubule-Associated Proteins; C472312:PCGF6 protein, human; C456544:STARD4 protein, human; D063150:Polycomb Repressive Complex 1; C095367:FASTK protein, human; D016044:Fusion Proteins, bcr-abl; D017346:Protein Serine-Threonine Kinases
keywords: cancer; cancer stem cells; minimum residual disease; personalized medicine; risk stratification