title: The genomic landscape of hypodiploid acute lymphoblastic leukemia.
abstract: The genetic basis of hypodiploid acute lymphoblastic leukemia (ALL), a subtype of ALL characterized by aneuploidy and poor outcome, is unknown. Genomic profiling of 124 hypodiploid ALL cases, including whole-genome and exome sequencing of 40 cases, identified two subtypes that differ in the severity of aneuploidy, transcriptional profiles and submicroscopic genetic alterations. Near-haploid ALL with 24-31 chromosomes harbor alterations targeting receptor tyrosine kinase signaling and Ras signaling (71%) and the lymphoid transcription factor gene IKZF3 (encoding AIOLOS; 13%). In contrast, low-hypodiploid ALL with 32-39 chromosomes are characterized by alterations in TP53 (91.2%) that are commonly present in nontumor cells, IKZF2 (encoding HELIOS; 53%) and RB1 (41%). Both near-haploid and low-hypodiploid leukemic cells show activation of Ras-signaling and phosphoinositide 3-kinase (PI3K)-signaling pathways and are sensitive to PI3K inhibitors, indicating that these drugs should be explored as a new therapeutic strategy for this aggressive form of leukemia.
authors: Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors: Linda
authors: L
authors: Holmfeldt
authors: Lei
authors: L
authors: Wei
authors: Ernesto
authors: E
authors: Diaz-Flores
authors: Michael
authors: M
authors: Walsh
authors: Jinghui
authors: J
authors: Zhang
authors: Li
authors: L
authors: Ding
authors: Debbie
authors: D
authors: Payne-Turner
authors: Michelle
authors: M
authors: Churchman
authors: Anna
authors: A
authors: Andersson
authors: Shann-Ching
authors: SC
authors: Chen
authors: Kelly
authors: K
authors: McCastlain
authors: Jared
authors: J
authors: Becksfort
authors: Jing
authors: J
authors: Ma
authors: Gang
authors: G
authors: Wu
authors: Samir N
authors: SN
authors: Patel
authors: Susan L
authors: SL
authors: Heatley
authors: Letha A
authors: LA
authors: Phillips
authors: Guangchun
authors: G
authors: Song
authors: John
authors: J
authors: Easton
authors: Matthew
authors: M
authors: Parker
authors: Xiang
authors: X
authors: Chen
authors: Michael
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authors: Rusch
authors: Kristy
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authors: Boggs
authors: Bhavin
authors: B
authors: Vadodaria
authors: Erin
authors: E
authors: Hedlund
authors: Christina
authors: C
authors: Drenberg
authors: Sharyn
authors: S
authors: Baker
authors: Deqing
authors: D
authors: Pei
authors: Cheng
authors: C
authors: Cheng
authors: Robert
authors: R
authors: Huether
authors: Charles
authors: C
authors: Lu
authors: Robert S
authors: RS
authors: Fulton
authors: Lucinda L
authors: LL
authors: Fulton
authors: Yashodhan
authors: Y
authors: Tabib
authors: David J
authors: DJ
authors: Dooling
authors: Kerri
authors: K
authors: Ochoa
authors: Mark
authors: M
authors: Minden
authors: Ian D
authors: ID
authors: Lewis
authors: L Bik
authors: LB
authors: To
authors: Paula
authors: P
authors: Marlton
authors: Andrew W
authors: AW
authors: Roberts
authors: Gordana
authors: G
authors: Raca
authors: Wendy
authors: W
authors: Stock
authors: Geoffrey
authors: G
authors: Neale
authors: Hans G
authors: HG
authors: Drexler
authors: Ross A
authors: RA
authors: Dickins
authors: David W
authors: DW
authors: Ellison
authors: Sheila A
authors: SA
authors: Shurtleff
authors: Ching-Hon
authors: CH
authors: Pui
authors: Raul C
authors: RC
authors: Ribeiro
authors: Meenakshi
authors: M
authors: Devidas
authors: Andrew J
authors: AJ
authors: Carroll
authors: Nyla A
authors: NA
authors: Heerema
authors: Brent
authors: B
authors: Wood
authors: Michael J
authors: MJ
authors: Borowitz
authors: Julie M
authors: JM
authors: Gastier-Foster
authors: Susana C
authors: SC
authors: Raimondi
authors: Elaine R
authors: ER
authors: Mardis
authors: Richard K
authors: RK
authors: Wilson
authors: James R
authors: JR
authors: Downing
authors: Stephen P
authors: SP
authors: Hunger
authors: Mignon L
authors: ML
authors: Loh
authors: Charles G
authors: CG
authors: Mullighan
mesh_terms: D000782:Aneuploidy; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D015972:Gene Expression Regulation, Neoplastic; D006238:Haploidy; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014183:Transplantation, Heterologous; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: C111431:IKZF2 protein, human; D016160:Retinoblastoma Protein; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051740:Ikaros Transcription Factor; D019869:Phosphatidylinositol 3-Kinases