title: A novel infant acute lymphoblastic leukemia cell line with MLL-AF5q31 fusion transcript.
abstract: Infant acute lymphoblastic leukemia (ALL) is characterized by the presence of the proB phenotype (CD10(-)/CD19(+)), poor prognosis and frequent rearrangement of the mixed lineage leukemia (MLL) gene. The most frequent rearrangement is t(4;11)(q21;q23), the role of whose product, the MLL-AF4 fusion transcript, has been extensively studied in leukemogenesis. In a cell line of infant leukemia with MLL rearrangement denoted KP-L-RY, panhandle PCR amplification of cDNA revealed the presence of a fusion transcript, MLL-AF5q31, indicating that AF5q31 is also a partner gene of MLL. In this fusion transcript the MLL exon 6 is fused in frame to the 5' side of the putative transactivation domain of AF5q31. The AF5q31 protein is a member of the AF4/LAF4/FMR2-related family of proteins, which have been suggested to play a role in hematopoietic cell growth and differentiation. The MLL-AF5q31 fusion transcript, although probably rare, appears to be associated with the pathogenesis of infant ALL like MLL-AF4. Co-expression of HoxA9 and Meis1 genes in the KP-L-RY cell line indicated possible functional similarity between MLL-AF4 and MLL-AF5q31. Further understanding of the function of AF5q31 as well as the specific leukemogenic mechanism of MLL-AF5q31 awaits future studies.
authors.affiliation: Department of Pediatrics, Kyoto Prefectural University of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Imamura
authors.forename: A
authors.initials: A
authors.lastname: Morimoto
authors.forename: S
authors.initials: S
authors.lastname: Ikushima
authors.forename: N
authors.initials: N
authors.lastname: Kakazu
authors.forename: S
authors.initials: S
authors.lastname: Hada
authors.forename: Y
authors.initials: Y
authors.lastname: Tabata
authors.forename: T
authors.initials: T
authors.lastname: Yagi
authors.forename: T
authors.initials: T
authors.lastname: Inaba
authors.forename: S
authors.initials: S
authors.lastname: Hibi
authors.forename: T
authors.initials: T
authors.lastname: Sugimoto
authors.forename: S
authors.initials: S
authors.lastname: Imashuku
mesh_terms: D000208:Acute Disease; D019677:Artificial Gene Fusion; D014408:Biomarkers, Tumor / Q000235:genetics*; D015139:Blotting, Southern; D002460:Cell Line; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D005091:Exons; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D051788:Myeloid-Lymphoid Leukemia Protein; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D014408:Biomarkers, Tumor; D017931:DNA Primers; D004273:DNA, Neoplasm; D018398:Homeodomain Proteins; C000616391:MEIS1 protein, human; C113855:MLL-AF4 fusion protein, human; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; C097899:homeobox protein HOXA9; D051788:Myeloid-Lymphoid Leukemia Protein