title: Coexistence of ETV6/RUNX1 and MLL aberrations in B-cell precursor acute lymphoblastic leukemia discloses a small subclass of BCP-ALL.
abstract: Out of 76 pediatric cases of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) positive for ETV6/RUNX1 (previously TEL/AML1) resulting from t(12;21), 7 cases revealed coexistence of ETV6/RUNX1 and MLL aberrations. One case of der(21) duplication with ETV6/RUNX1 exhibited a novel MLL translocation variant t(6;11)(p21.1p23;q13q25), with translocation of 3' telomeric MLL and deletion of 5' centromeric MLL. Another case of der(21) duplication with ETV6/RUNX1 showed MLL rearrangement upon Southern blotting. The remaining five ETV6/RUNX1-positive cases had MLL allelic deletion. ETV6/RUNX1 and MLL aberration clone size in these cases was suggestive of ETV6/RUNX1 as an early primary event, originating in the embryonic or infant stage and developing into leukemia by later acquisition of MLL aberration, ETV6 loss, and ETV6/RUNX1 duplication as secondary events. To date, the prognosis has been favorable, which seems to be compatible with ETV6/RUNX1-positive ALL. We conclude that the cases with coexisting ETV6/RUNX1 and MLL aberrations probably exist as a small, hidden group of ETV6/RUNX1-positive BCP-ALL, which invites further investigation, in large series from different populations, to confirm the findings and establish the biological mechanisms and prognostic significance.
authors.affiliation: Cancer Cytogenetics Laboratory, Tata Memorial Hospital, Parel, Mumbai 400012, India. pratibha.amare@gmail.com
authors.forename: Pratibha S
authors.initials: PS
authors.lastname: Amare Kadam
authors.forename: Gauri Chandrakant
authors.initials: GC
authors.lastname: Raje
authors.forename: Anurita Peter
authors.initials: AP
authors.lastname: Pais
authors.forename: Shripad
authors.initials: S
authors.lastname: Banavali
mesh_terms: D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D005260:Female; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000145:classification / Q000235:genetics*; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D011495:Histone-Lysine N-Methyltransferase; D051788:Myeloid-Lymphoid Leukemia Protein; D015514:Oncogene Proteins, Fusion; C497422:KMT2A protein, human; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein