title: Ph-like acute lymphoblastic leukemia with a novel PAX5-KIDINS220 fusion transcript.
abstract: Although "paired box 5" (PAX5)-related fusion genes are well documented in childhood B-cell precursor acute lymphoblastic leukemia (ALL), these types of fusion with the exception of PAX5-JAK2 are rarely seen in patients with gene expression profiles similar to those of BCR-ABL1 (Philadelphia)-positive ALL (Ph-like ALL). We report a novel fusion of the genes PAX5 and "kinase D-interacting substrate of 220 kDa" (KIDINS220, also known as ARMS) in a Ph-like ALL. As PAX5 is a master regulator of B-lymphocyte differentiation, PAX5 rearrangements induce a differentiation block in B lymphocytes. KIDINS220 is a mediator of multiple receptor signaling pathways, interacts with both T- and B-cell receptors, and is necessary for sustained extracellular signal-regulated kinase (ERK) signaling. Although functional studies are needed, the PAX5-KIDINS220 fusion protein might not only inhibit wild-type PAX5 function, but also promote sustained activation of the ERK signaling pathway through upregulation of KIDINS220. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan.
authors.forename: Kenichi
authors.identifier: 0000-0003-1499-538X
authors.initials: K
authors.lastname: Sakamoto
authors.affiliation: Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Imamura
authors.affiliation: Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan.
authors.forename: Takuyo
authors.initials: T
authors.lastname: Kanayama
authors.affiliation: Department of Pediatrics, National Hospital Organization Maizuru Medical Center, Japan.
authors.forename: Mio
authors.initials: M
authors.lastname: Yano
authors.affiliation: Department of Pediatrics, Japanese Red Cross Kyoto Daini Hospital, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Asai
authors.affiliation: Department of Pediatrics, Mie University, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Deguchi
authors.affiliation: Department of Pediatrics, Osaka University, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Hashii
authors.affiliation: Department of Pediatrics, University of Fukui, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Tanizawa
authors.affiliation: Department of Pediatrics, University of Fukui, Japan.
authors.forename: Yusei
authors.initials: Y
authors.lastname: Ohshima
authors.affiliation: Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Kiyokawa
authors.affiliation: Clinical Research Center, National Hospital Organization Nagoya Medical Center, Japan.
authors.forename: Keizo
authors.initials: K
authors.lastname: Horibe
authors.affiliation: Department of Hematology/Oncology, Miyagi Children's Hospital, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sato
mesh_terms: D002648:Child; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D051757:PAX5 Transcription Factor / Q000235:genetics*; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D011379:Prognosis
chemical_list: C482591:KIDINS220 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D015514:Oncogene Proteins, Fusion; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human