title: A Rare Case of Acute Myeloid Leukemia with a t(2;3) Chromosomal Translocation Characterized by Thrombophilia and Chemoresistance.
abstract: We hereby report a case of acute myeloid leukemia with translocation t(2;3) and involvement of the ectopic virus integration site-1 (EVI1) gene. Like most other 3q26-related disorders reported thus far, we describe a phenotype with elevated platelet counts and dysmegakaryopoesis. The clinical course of our patient was complicated by symptomatic thrombophilia and chemoresistance. In addition, our case exhibited FLT3 (Fms-related tyrosine kinase 3) internal tandem duplication. Although anagrelide was successful in controlling elevated platelet counts, allogeneic stem cell transplantation failed to overcome chemoresistance due to simultaneous graft-versus-host-disease and relapse of acute myeloid leukemia. Given the dismal outcome of our case and previously reported cases, we propagate the implementation of targeted therapies to newly diagnosed patients with acute myeloid leukemia t(2;3). Preclinical models indicate drugs that plausibly target the EVI1-related molecular vulnerability as candidates for basket trials. Anagrelide exhibited a hopeful signal of activity in 3q26-related thrombocytosis and should be evaluated for implementation as supportive care.
authors.affiliation: Charité Campus Mitte, Medizinische Klinik mit Schwerpunkt Onkologie und Hämatologie.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Bozzetti
authors.forename: Seval
authors.initials: S
authors.lastname: Türkmen
authors.forename: Ulrich
authors.initials: U
authors.lastname: Richter
authors.forename: Lars
authors.initials: L
authors.lastname: Fransecky
authors.forename: Gürkan
authors.initials: G
authors.lastname: Bal
authors.forename: Carsten-Oliver
authors.initials: CO
authors.lastname: Schulz
authors.forename: Philipp
authors.initials: P
authors.lastname: Hemmati
authors.forename: Renate
authors.initials: R
authors.lastname: Arnold
authors.forename: Hanno
authors.initials: H
authors.lastname: Riess
authors.forename: Philipp
authors.initials: P
authors.lastname: le Coutre
mesh_terms: D001792:Blood Platelets / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000150:complications* / Q000235:genetics* / Q000628:therapy; D000074008:MDS1 and EVI1 Complex Locus Protein; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D010976:Platelet Count; D011519:Proto-Oncogenes / Q000235:genetics*; D011799:Quinazolines / Q000627:therapeutic use; D033581:Stem Cell Transplantation; D019851:Thrombophilia / Q000150:complications* / Q000188:drug therapy; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D010975:Platelet Aggregation Inhibitors; D011799:Quinazolines; D014157:Transcription Factors; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3; C021139:anagrelide