title: Coexistence of iAMP21 andETV6-RUNX1fusion in an adolescent with B cell acute lymphoblastic leukemia: literature review of six additional cases.
abstract: BACKGROUND
  Intrachromosomal amplification of chromosome 21 (iAMP21) results from breakage-fusion-bridge cycles and chromothripsis is a distinct marker of a subgroup of B cell acute lymphoblastic leukemia (B-ALL) cases associated with a poor prognosis. iAMP21 accounts for 2% of pediatric B-ALL and occurs predominantly in older children or adolescents.ETV6-RUNX1fusion, resulting from t(12;21)(p13;q22), is associated with an excellent outcome in younger children with B-ALL. Coexistence of iAMP21 withETV6-RUNX1fusion is extremely rare with limited clinical information available.
  
  
  RESULTS
  We report the case of an 18-year old Caucasian man diagnosed withETV6-RUNX1fusion positive B-ALL. He was treated with intensive chemotherapy and achieved remission for 6 months before relapse, 15 months after the initial diagnosis. G-band karyotyping and Fluorescence in situ hybridization (FISH) analyses performed on bone marrow revealed complex abnormalities: 41,X,-Y,der(3)t(3;20)(p11.2;q11.2),-4,t(5;22)(q32;q11.2),del(9)(p13),dic(9;17)(p13;p11.2),t(12;21)(p13;q22),der(14)t(14;17)(p11.2;q11.2),der(17;22)(q11.2;q11.2),-20,add(21)(q22),-22[4]/46,XY[15] with an iAMP21 and anETV6-RUNX1. Additional molecular studies confirmedETV6-RUNX1fusion and with aTP53mutation. High-resolution single nucleotide polymorphism microarray (SNP array) revealed the iAMP21 to be chromothripsis of 21q and subsequent metaphase FISH further delineated complex genomic aberrations. Although the patient received intensive chemotherapy with allogenic stem cell transplant, he died 26 months after initial diagnosis. We searched the literature and identified six cases showing coexisting iAMP21 andETV6-RUNX1. The median age for these six patients was 10 years (range, 2-18) and males predominated. The median overall survival (OS) was 28 months.
  
  
  CONCLUSIONS
  Patients with B-ALL associated with both iAMP21 andETV6-RUNX1tend to be older children or adolescents and have a poor prognosis.
authors.affiliation: School of Health Professions, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 0002, Houston, TX 77030 USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 0350, Houston, TX 77030 USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Reynolds
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 0149, Houston, TX 77030 USA ; Department of Oncology, Jiangsu Hospital of Traditional Chinese Medicine, Nanjing, Jiangsu China.
authors.forename: Lianghua
authors.initials: L
authors.lastname: Fang
authors.affiliation: School of Health Professions, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 0002, Houston, TX 77030 USA.
authors.forename: Corrie
authors.initials: C
authors.lastname: DeGraffenreid
authors.affiliation: School of Health Professions, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 0002, Houston, TX 77030 USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Sterns
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 0149, Houston, TX 77030 USA.
authors.forename: Keyur P
authors.initials: KP
authors.lastname: Patel
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 0072, Houston, TX 77030 USA.
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 0072, Houston, TX 77030 USA.
authors.forename: Pei
authors.initials: P
authors.lastname: Lin
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 0350, Houston, TX 77030 USA ; Department of Pathology, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Tarry 7-723, Chicago, IL 60611 USA.
authors.forename: Xinyan
authors.initials: X
authors.lastname: Lu
keywords: B-ALL; ETV6-RUNX1 fusion; RUNX1 amplification; SNP microarray; iAMP21