title: Genomic analysis of adult B-ALL identifies potential markers of shorter survival.
abstract: B lymphoblastic leukemia (B-ALL) in adults has a higher risk of relapse and lower long-term survival than pediatric B-ALL, but data regarding genetic prognostic biomarkers are much more limited for adult patients. We identified 70 adult B-ALL patients from three institutions and performed genome-wide analysis via single nucleotide polymorphism (SNP) arrays on DNA isolated from their initial diagnostic sample and, when available, relapse bone marrow specimens to identify recurring copy number alterations (CNA). As B-cell developmental genes play a crucial role in this leukemia, we assessed such for recurrent deletions in diagnostic and relapse samples. We confirmed previous findings that the most prevalent deletions of these genes occur in CDKN2A, IKZF1, and PAX5, with several others at lower frequencies. Of the 16 samples having paired diagnostic and relapse samples, 5 showed new deletions in these recurrent B-cell related genes and 8 showed abolishment. Deletion of EBF1 heralded a significant negative prognostic impact on relapse free survival in univariate and multivariate analyses. The combination of both a CDKN2A/B deletion and an IKZF1 alteration (26% of cases) also showed a trend toward predicting worse overall survival compared to having only one or neither of these deletions. These findings add to the understanding of genomic influences on this comparably understudied disease cohort that upon further validation may help identify patients who would benefit from upfront treatment intensification.
authors.affiliation: Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112, USA. Electronic address: shiven.patel@hci.utah.edu.
authors.forename: Shiven
authors.initials: S
authors.lastname: Patel
authors.affiliation: Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112, USA; Department of Pediatrics, University of Utah, Salt Lake City, UT, USA. Electronic address: clint.mason@hsc.utah.edu.
authors.forename: Clinton C
authors.initials: CC
authors.lastname: Mason
authors.affiliation: Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112, USA. Electronic address: martha.glenn@hci.utah.edu.
authors.forename: Martha J
authors.initials: MJ
authors.lastname: Glenn
authors.affiliation: ARUP Institute for Clinical and Experimental Pathology, 500 Chipeta Way, Salt Lake City, UT 84108, USA. Electronic address: Christian.n.paxton@aruplab.com.
authors.forename: Christian N
authors.initials: CN
authors.lastname: Paxton
authors.affiliation: ARUP Institute for Clinical and Experimental Pathology, 500 Chipeta Way, Salt Lake City, UT 84108, USA; University of Utah Department of Pathology, 15N Medical Dr E, JMRB Rm2100, Salt Lake City, UT 84112, USA. Electronic address: sarah.south@aruplab.com.
authors.forename: Sara T
authors.initials: ST
authors.lastname: South
authors.affiliation: Intermountain Healthcare Central Region Department of Pathology, 8th Avenue and C Street, Salt Lake City, UT 84143, USA; Intermountain Healthcare BioRepository, 8th Avenue and C Street, Salt Lake City, UT 84143, USA. Electronic address: Melissa.Cessna@imail2.org.
authors.forename: Melissa H
authors.initials: MH
authors.lastname: Cessna
authors.affiliation: Intermountain Blood and Marrow Transplant/Acute Leukemia Program, LDS Hospital, 8th Avenue and C Street, Salt Lake City, UT 84143, USA. Electronic address: Julie.asch@imail.org.
authors.forename: Julie
authors.initials: J
authors.lastname: Asch
authors.affiliation: University of Michigan Department of Hematology, Ann Arbor, MI, USA. Electronic address: ecobain@med.umich.edu.
authors.forename: Erin F
authors.initials: EF
authors.lastname: Cobain
authors.affiliation: University of Michigan Department of Hematology, Ann Arbor, MI, USA. Electronic address: dbixby@med.umich.edu.
authors.forename: Dale L
authors.initials: DL
authors.lastname: Bixby
authors.affiliation: University of Michigan Department of Pathology, 1301 Catherine St, Ann Arbor, MI 48109, USA. Electronic address: lbsmith@med.umich.edu.
authors.forename: Lauren B
authors.initials: LB
authors.lastname: Smith
authors.affiliation: Nationwide Children's Hospital, Department of Pathology and Laboratory Medicine, 700 Children's Drive, Room C0839, Columbus, OH 43205, USA; Ohio State University College of Medicine, Department of Pathology, Columbus, OH 43210, USA. Electronic address: Shalini.Reshmi@nationwidechildrens.org.
authors.forename: Shalini
authors.initials: S
authors.lastname: Reshmi
authors.affiliation: Nationwide Children's Hospital, Department of Pathology and Laboratory Medicine, 700 Children's Drive, Room C0839, Columbus, OH 43205, USA; Ohio State University College of Medicine, Department of Pathology, Columbus, OH 43210, USA; Ohio State University College of Medicine, Department of Pediatrics, Columbus, OH 43210, USA. Electronic address: Julie.Gastier-Foster@nationwidechildrens.org.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Gastier-Foster
authors.affiliation: Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112, USA; Department of Pediatrics, University of Utah, Salt Lake City, UT, USA. Electronic address: joshua.schiffman@hci.utah.edu.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Schiffman
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, UT, USA; ARUP Institute for Clinical and Experimental Pathology, 500 Chipeta Way, Salt Lake City, UT 84108, USA; University of Utah Department of Pathology, 15N Medical Dr E, JMRB Rm2100, Salt Lake City, UT 84112, USA. Electronic address: rodney.miles@path.utah.edu.
authors.forename: Rodney R
authors.initials: RR
authors.lastname: Miles
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D056915:DNA Copy Number Variations; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D023281:Genomics / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000401:mortality*; D011379:Prognosis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D005819:Genetic Markers
keywords: Acute lymphoblastic leukemia; B-cell; CDKN2A; Copy number abnormalities; Genome-wide association study; IKZF1