title: High incidence of t(7;12)(q36;p13) in infant AML but not in infant ALL, with a dismal outcome and ectopic expression of HLXB9.
abstract: The t(7;12)(q36;p13) is a recurrent translocation involving the ETV6/TEL gene (12p13) and a heterogeneous breakpoint at 7q36. A fusion transcript between HLXB9 and ETV6 in AML with t(7;12) is occasionally found. To study the incidence of t(7;12) in infant and childhood acute leukemia, we screened 320 cases <36 months using FISH. Additionally, 28 pediatric cases >36 months with cytogenetic breakpoints at 12p and 7q were investigated. We studied the presence of an HXLB9-ETV6 fusion transcript and quantified the expression of various genes located in the 7q36 breakpoint region. In total, six AML patients carried the t(7;12) of which five were infants and one child of 18 months. Only one out of 99 infant ALL patients harbored the t(7;12). No t(7;12) was found in older children with AML or ALL. AML patients carrying a t(7;12) had a poor outcome with a 3-year EFS of 0%. A fusion of HLXB9 to ETV6 was found in four AML cases with t(7;12). The 7q36 genes NOM1, LMBR1, RNF32, and SHH were equally expressed among t(7;12)-positive AML versus t(7;12)-negative AML, t(7;12)-negative ALL, or normal bone marrow. However, the HLXB9 expression was highly increased in t(7;12)-positive cases, including those with an HLXB9-ETV6 fusion. We conclude that the t(7;12) is almost exclusively present in infant AML and covers 30% of infant AML, while it is extremely rare in infant ALL and older children. The t(7;12) is associated with a poor outcome and an ectopic expression of HLXB9 is commonly involved in this genetic subtype of leukemia.
authors.affiliation: Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands. a.vonbergh@erasmusmc.nl
authors.forename: Anne R M
authors.initials: AR
authors.lastname: von Bergh
authors.forename: Ellen
authors.initials: E
authors.lastname: van Drunen
authors.forename: Elisabeth R
authors.initials: ER
authors.lastname: van Wering
authors.forename: Laura J C M
authors.initials: LJ
authors.lastname: van Zutven
authors.forename: Ina
authors.initials: I
authors.lastname: Hainmann
authors.forename: Gudmar
authors.initials: G
authors.lastname: Lönnerholm
authors.forename: Jules P
authors.initials: JP
authors.lastname: Meijerink
authors.forename: Rob
authors.initials: R
authors.lastname: Pieters
authors.forename: H Berna
authors.initials: HB
authors.lastname: Beverloo
mesh_terms: D000208:Acute Disease; D002675:Child, Preschool; D019457:Chromosome Breakage; D002881:Chromosomes, Human, Pair 12; D002897:Chromosomes, Human, Pair 7; D015331:Cohort Studies; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D007951:Leukemia, Myeloid / Q000235:genetics*; D008297:Male; D008957:Models, Genetic; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014178:Translocation, Genetic; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D018398:Homeodomain Proteins; D015514:Oncogene Proteins, Fusion; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D014157:Transcription Factors; D000097764:ETS Translocation Variant 6 Protein; C490003:MNX1 protein, human