title: Genetic and clinical characterization of 45 acute leukemia patients with MLL gene rearrangements from a single institution.
abstract: Chromosomal rearrangements affecting the MLL gene are associated with high-risk pediatric, adult and therapy-associated acute leukemia. In this study, conventional cytogenetic, fluorescence in situ hybridization, and molecular genetic studies were used to characterize the type and frequency of MLL rearrangements in a consecutive series of 45 Portuguese patients with MLL-related leukemia treated in a single institution between 1998 and 2011. In the group of patients with acute lymphoblastic leukemia and an identified MLL fusion partner, 47% showed the presence of an MLL-AFF1 fusion, as a result of a t(4;11). In the remaining cases, a MLL-MLLT3 (27%), a MLL-MLLT1 (20%), or MLL-MLLT4 (7%) rearrangement was found. The most frequent rearrangement found in patients with acute myeloid leukemia was the MLL-MLLT3 fusion (42%), followed by MLL-MLLT10 (23%), MLL-MLLT1 (8%), MLL-ELL (8%), MLL-MLLT4 (4%), and MLL-MLLT11 (4%). In three patients, fusions involving MLL and a septin family gene (SEPT2, SEPT6, and SEPT9), were identified. The most frequently identified chromosomal rearrangements were reciprocal translocations, but insertions and deletions, some cryptic, were also observed. In our series, patients with MLL rearrangements were shown to have a poor prognosis, regardless of leukemia subtype. Interestingly, children with 1 year or less showed a statistically significant better overall survival when compared with both older children and adults. The use of a combined strategy in the initial genetic evaluation of acute leukemia patients allowed us to characterize the pattern of MLL rearrangements in our institution, including our previous discovery of two novel MLL fusion partners, the SEPT2 and CT45A2 genes, and a very rare MLL-MLLT4 fusion variant.
authors: Department of Genetics, Portuguese Oncology Institute, Porto, Portugal.
authors: Nuno
authors: N
authors: Cerveira
authors: Susana
authors: S
authors: Lisboa
authors: Cecília
authors: C
authors: Correia
authors: Susana
authors: S
authors: Bizarro
authors: Joana
authors: J
authors: Santos
authors: Lurdes
authors: L
authors: Torres
authors: Joana
authors: J
authors: Vieira
authors: João D
authors: JD
authors: Barros-Silva
authors: Dulcineia
authors: D
authors: Pereira
authors: Cláudia
authors: C
authors: Moreira
authors: Claus
authors: C
authors: Meyer
authors: Tereza
authors: T
authors: Oliva
authors: Ilídia
authors: I
authors: Moreira
authors: Ângelo
authors: Â
authors: Martins
authors: Luísa
authors: L
authors: Viterbo
authors: Vítor
authors: V
authors: Costa
authors: Rolf
authors: R
authors: Marschalek
authors: Armando
authors: A
authors: Pinto
authors: José M
authors: JM
authors: Mariz
authors: Manuel R
authors: MR
authors: Teixeira
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007223:Infant; D016547:Kinesins / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D009218:Myosins / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011379:Prognosis; D014157:Transcription Factors / Q000235:genetics; D035602:Transcriptional Elongation Factors; D055815:Young Adult
chemical_list: C095516:AFDN protein, human; D004268:DNA-Binding Proteins; C529663:MLL-MLLT3 fusion protein, human; C081448:MLLT1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors; D051788:Myeloid-Lymphoid Leukemia Protein; C081449:AFF1 protein, human; D009218:Myosins; D016547:Kinesins