title: HOXA9 and MEIS1 gene overexpression in the diagnosis of childhood acute leukemias: Significant correlation with relapse and overall survival.
abstract: Homeobox genes HOXA9 and MEIS1 are evolutionarily conserved transcription factors with essential roles in both hematopoiesis and leukemogenesis. They act as dominant cooperating oncoproteins that cause acute leukemias bearing MLL translocations and to a lesser extent T-cell acute lymphocytic leukemia (ALL) characterized by other gene fusions. Overexpression is associated with an adverse prognosis in adults. In childhood, the genes have only been investigated in leukemias bearing MLL translocations. The aim of this study was to determine whether overexpression extends to leukemic subtypes other than the MLL-positive subtype in childhood. We use quantitative real-time PCR methodology to investigate gene expression in 100 children with acute leukemias and compare them to those of healthy controls. We show that abnormally high HOXA9 and MEIS1 gene expression is associated with a variety of leukemic subtypes, including various maturation stages of B-cell ALL and cytogenetic types other than the MLL-positive population, thus suggesting that the genes are implicated in the development of a broad range of leukemic subtypes in childhood. In addition, we show that HOXA9 and MEIS1 overexpression are inversely correlated with relapse and overall survival, so the genes could become useful predictive markers of the clinical course of pediatric acute leukemias.
authors.affiliation: Pediatric Hematology/Oncology Unit, First Department of Pediatrics, University of Athens, "Aghia Sofia" Children's Hospital, 11527 Athens, Greece. Electronic address: madamaki@med.uoa.gr.
authors.forename: Maria
authors.initials: M
authors.lastname: Adamaki
authors.affiliation: Pediatric Hematology/Oncology Unit, First Department of Pediatrics, University of Athens, "Aghia Sofia" Children's Hospital, 11527 Athens, Greece.
authors.forename: George I
authors.initials: GI
authors.lastname: Lambrou
authors.affiliation: Pediatric Hematology/Oncology Unit, First Department of Pediatrics, University of Athens, "Aghia Sofia" Children's Hospital, 11527 Athens, Greece.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Athanasiadou
authors.affiliation: Pediatric Hematology/Oncology Unit, First Department of Pediatrics, University of Athens, "Aghia Sofia" Children's Hospital, 11527 Athens, Greece.
authors.forename: Spiros
authors.initials: S
authors.lastname: Vlahopoulos
authors.affiliation: Department of Biological Chemistry, University of Athens Medical School, 11527 Athens, Greece.
authors.forename: Athanasios G
authors.initials: AG
authors.lastname: Papavassiliou
authors.affiliation: Pediatric Hematology/Oncology Unit, First Department of Pediatrics, University of Athens, "Aghia Sofia" Children's Hospital, 11527 Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Moschovi
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D012008:Recurrence; D016019:Survival Analysis; D015854:Up-Regulation / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; C000616391:MEIS1 protein, human; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; C097899:homeobox protein HOXA9
keywords: Childhood leukemia; Gene overexpression; HOXA9; MEIS1; Overall survival; Relapse