title: Clonal eosinophils are a morphologic hallmark of ETV6/ABL1 positive acute myeloid leukemia.
abstract: OBJECTIVE
  The ETV6 gene undergoes rearrangements with tyrosine kinases in hematologic malignancies and solid tumors. ETV6/ABL1 chimeric proteins have been detected both in lymphoid and myeloid disorders. Our objective was to study two new cases of ETV6/ABL1-positive acute myeloid leukemia (AML) and to focus on bone marrow morphology and on molecular cytogenetics of eosinophilic cells.
  
  
  METHODS
  Fluorescence in situ hybridization (FISH) was performed in two AML cases with different translocations, i.e. t(8;12)(p21;p13) and t(9;12) (q34; p13). We used probes for the short arm of chromosome 12, for ABL1 and BCR, for centromeric regions, and for whole chromosome arms. Polymerase chain reaction (PCR) was carried out by applying primers selected for the ETV6 gene.
  
  
  RESULTS
  In both cases, bone marrow morphology was characterized by trilineage dysplasia and increased abnormal eosinophils. FISH showed the 5'ETV6 translocated to chromosome 8 in patient #1, and to chromosome 9 in patient #2. A 3' PCR identified chimeric products resulting from fusion between ETV6 exon 4 or exon 5, and ABL1 exon 2. Accordingly, an ETV6/ABL1 fusion signal was detected on der(8) in patient #1, and on der(9) in patient #2. Using interphase FISH abnormal bone marrow eosinophils were proved to belong to the neoplastic clone, carrying the ETV6 rearrangement.
  
  
  CONCLUSIONS
  Our findings provide new information on the heterogeneity of conventional cytogenetics in ETV6/ABL1 positive leukemias, and indicate the putative target cell in this AML is an immature precursor capable of terminally differentiating towards eosinophils.
authors.affiliation: Hematology and Bone Marrow Transplantation Unit, Policlinico Monteluce, University of Perugia, via Brunamonti, 06122 Perugia, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: La Starza
authors.forename: Maurizio
authors.initials: M
authors.lastname: Trubia
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Testoni
authors.forename: Emanuela
authors.initials: E
authors.lastname: Ottaviani
authors.forename: Elena
authors.initials: E
authors.lastname: Belloni
authors.forename: Barbara
authors.initials: B
authors.lastname: Crescenzi
authors.forename: Massimo
authors.initials: M
authors.lastname: Martelli
authors.forename: Georges
authors.initials: G
authors.lastname: Flandrin
authors.forename: Pier Giuseppe
authors.initials: PG
authors.lastname: Pelicci
authors.forename: Cristina
authors.initials: C
authors.lastname: Mecucci
mesh_terms: D000328:Adult; D000754:Anemia, Refractory, with Excess of Blasts / Q000150:complications; D001853:Bone Marrow / Q000473:pathology; D019070:Cell Lineage; D002869:Chromosome Aberrations; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics* / Q000648:ultrastructure; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics / Q000648:ultrastructure; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics / Q000648:ultrastructure; D002999:Clone Cells / Q000201:enzymology / Q000473:pathology; D004802:Eosinophilia / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D004804:Eosinophils / Q000201:enzymology / Q000473:pathology*; D016313:Genes, abl; D018740:Genetic Heterogeneity; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000097:blood* / Q000150:complications / Q000235:genetics; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000201:enzymology / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000502:physiology; D011505:Protein-Tyrosine Kinases; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D014178:Translocation, Genetic / Q000235:genetics*; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D015514:Oncogene Proteins, Fusion; D011505:Protein-Tyrosine Kinases; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C426234:TEL-ABL fusion protein, human; D000097764:ETS Translocation Variant 6 Protein