title: Pediatric chronic myeloid leukemia with inv(3)(q21q26.2) and T lymphoblastic transformation: a case report.
abstract: BACKGROUND
  Chronic myeloid leukemia (CML) comprises ~3 % of pediatric leukemia. Although therapy with tyrosine kinase inhibitors (TKIs) is highly effective for CML, multiple factors have been identified as predictive of treatment failure. Chromosomal abnormalities involving the MECOM locus at 3q26 portend therapy resistant disease in adults, yet have never been described in pediatric patients and have not been associated with T lymphoblastic progression.
  
  
  METHODS
  We present a case of an 11-year-old boy with CML possessing the unique combination of T lymphoblastic transformation and a subclone harboring inv(3)(q21q26.2) at diagnosis. This is the first reported case of pediatric CML with inv(3)(q21q26.2) and the first case of T lymphoblastic progression associated with this karyotype. The patient was treated with single agent TKI therapy with robust initial response. Marrow histology at one month showed restoration of trilineage hematopoiesis and BCR-ABL RT-PCR at three months showed a 1.4 log reduction in transcript levels.
  
  
  CONCLUSIONS
  The karyotypic abnormality of inv(3)(q21q26.2) in CML is not restricted to adult patients. Moreover, while chromosome 3 abnormalities are markers of TKI resistance in adults, our patient showed a robust early response to single agent TKI therapy. This finding suggests pediatric CML with inv(3)(q21q26.2) may have distinct features and more favorable treatment responses than those described in adults.
authors.affiliation: Department of Medicine, Boston Children's Hospital, Boston, Massachusetts USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Lewen
authors.affiliation: Nemours Center for Cancer and Blood Disorders, Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware USA.
authors.forename: Renee
authors.initials: R
authors.lastname: Gresh
authors.affiliation: Department of Pathology and Laboratory Medicine, Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Queenan
authors.affiliation: Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania USA ; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Paessler
authors.affiliation: Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania USA ; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania USA.
authors.forename: Vinodh
authors.initials: V
authors.lastname: Pillai
authors.affiliation: Department of Medicine, Division of Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hexner
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania USA.
authors.forename: Dale
authors.initials: D
authors.lastname: Frank
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Bagg
authors.affiliation: Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Aplenc
authors.affiliation: Nemours Center for Cancer and Blood Disorders, Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware USA.
authors.forename: Emi
authors.initials: E
authors.lastname: Caywood
authors.affiliation: Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania USA ; Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania USA.
authors.forename: Gerald
authors.initials: G
authors.lastname: Wertheim
keywords: Additional chromosomal abnormalities; Blast phase; Case report; Chronic myeloid leukemia; MECOM