title: Pediatric ALK+ anaplastic large cell lymphoma with t(3;8)(q26.2;q24) translocation and c-myc rearrangement terminating in a leukemic phase.
abstract: Pediatric ALK-positive anaplastic large cell lymphoma (ALK+ ALCL) is usually associated with a favorable prognosis. ALK+ ALCL associated with a leukemic phase is uncommon, but has been associated with an aggressive clinical course and unfavorable prognosis. Overexpression of c-myc has been shown to be a consistent finding in ALK+, but not ALK-negative ALCL (ALK- ALCL), and the c-myc gene is considered a downstream target of deregulated ALK signaling. We describe a pediatric ALK+ ALCL with a leukemic phase at relapse. Similar to other rare cases described in the literature, it followed an aggressive clinical course despite multiple regimens of chemotherapy and bone marrow transplantation. Lymphoma cells showed aberrant ALK expression and c-myc overexpression. In addition to the characteristic t(2;5)(p23;q35) translocation, a t(3;8)(q26.2;q24) translocation was also present, and c-myc gene rearrangement was confirmed by FISH analysis. The findings in this case demonstrate the association of peripheral blood leukemic involvement and aggressive clinical course, and suggest that other factors, such as c-myc rearrangement, may be responsible for the aggressive clinical behavior in ALK+ ALCL.
authors.affiliation: Department of Pathology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Monaco
authors.forename: Lawrence
authors.initials: L
authors.lastname: Tsao
authors.forename: V V
authors.initials: VV
authors.lastname: Murty
authors.forename: S V
authors.initials: SV
authors.lastname: Nandula
authors.forename: Virginia
authors.initials: V
authors.lastname: Donovan
authors.forename: J
authors.initials: J
authors.lastname: Oesterheld
authors.forename: Govind
authors.initials: G
authors.lastname: Bhagat
authors.forename: Bachir
authors.initials: B
authors.lastname: Alobeid
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D017809:Fatal Outcome; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases; D014178:Translocation, Genetic
chemical_list: D016271:Proto-Oncogene Proteins c-myc; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases