RESUMO
Rearrangement of the mixed lineage-leukemia gene (MLL-r) is common in hematological diseases and is generally associated with poor prognosis. The mixed-lineage leukemia gene translocated to, 3 (MLLT3) gene (9p22) is a frequent MLL-r partner (â¼18% of leukemias with MLL rearrangement) and is characterized by the translocation t(9;11) (p22;q23), forming an MLL-MLLT3 gene fusion. MLL-r are usually simple reciprocal translocations between two different chromosomes, although karyotypes with complex MLL-r have been observed. We present a rare case of a child with acute lymphoblastic leukemia with a complex karyotype in which the classical t(9;11) (p22;q23) was cryptically relocated into a third chromosome in a balanced three-way translocation. At the genome level, however, the MLL-MLLT3 three-way translocation still displayed both reciprocal fusion transcripts. This argues in favor for a model where a simple two-way t(9;11) (p22;q23) was likely the first step that then evolved in to a more complex karyotype. Multicolor banding techniques can be used to greatly refine complex karyotypes and its chromosomal breakpoints. Also in the presence of putative new rearrangements, Long distance inverse-PCR is an important tool to identify which gene fusion is involved.
Assuntos
Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Pré-Escolar , Feminino , Humanos , Cariótipo , Translocação GenéticaRESUMO
Translocations involving MLL gene are common among children with acute leukemias. Most importantly, the presence of a given MLL fusion partner dictates the outcome of patients. Patients with complex MLL rearrangements, e.g. three-way translocations could be related to a poor clinical outcome. For this purpose, we characterize 5 childhood patients with three-way translocations involving MLL gene. By LDI-PCR we identified 15 out of 17 fusion alleles and determined the localization of these breakpoints. In all cases at least one functional MLL fusion allele was present. In addition, patients displayed a remaining 3'-MLL allele that allow in principle the expression of the MLL* protein variant.
Assuntos
Leucemia Mieloide Aguda/genética , Proteína de Leucina Linfoide-Mieloide/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Translocação Genética , Sequência de Bases , Pré-Escolar , Feminino , Rearranjo Gênico , Histona-Lisina N-Metiltransferase , Humanos , Lactente , Masculino , Dados de Sequência Molecular , Proteínas de Fusão Oncogênica/genética , Reação em Cadeia da Polimerase/métodosRESUMO
High hyperdiploidy with modal chromosome numbers between 50 and 65 is common in childhood acute lymphoblastic leukemia (ALL), occurring in 25-30% of the cases. This chromosomal constitution is associated with a very good prognosis. By contrast, near triploidy and tetraploidy are found in <1% of childhood ALL. Given the sparseness of this group, the associated chromosomal abnormalities and their prognostic implications have not yet been studied in detail. Here, we describe clinical and molecular cytogenetic findings in a child with ALL who had a near-triploid complex karyotype, with loss and gain of chromosomes, including extra copies of the same derivative chromosomes. These findings suggest a random nondisjunction mechanism for near triploidy in the present case.
Assuntos
Aberrações Cromossômicas , Poliploidia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Criança , Feminino , Humanos , CariotipagemRESUMO
Hyperdiploidy is rarely observed in childhood acute myeloid leukemia (AML). Described here is the case of a 2(1/2)-year-old girl with AML-M5 and 51 chromosomes characterized by double tetrasomy of chromosomes 8 and 21 and also a neocentric derivative chromosome neo(1)(qter-->q23 approximately 24::q23 approximately 24-->q43-->neo-->q43-->qter). Little is known about the prognostic significance of these chromosomal abnormalities in childhood AML. In the actual case, complete remission was achieved after chemotherapy, which continued for 7 months. No acquired neocentric chromosome 1 has been described previously, even though neocentromere formation has been reported for other chromosomes in neoplasms.
Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 21 , Cromossomos Humanos Par 8 , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Pré-Escolar , Feminino , Humanos , Hibridização in Situ Fluorescente , CariotipagemRESUMO
Infants diagnosed with acute myelogenous leukemia (AML) are likely to have subtypes M4 or M5 characterized by 11q23 abnormalities like a t(9;11)(p22;q23). Detection of all possible types of chromosomal abnormalities, including mixed lineage leukemia (MLL) gene rearrangements at 11q23, is of importance for the identification of biological subgroups, which might differ in drug resistance and/or clinical outcome. Here, we report the clinical, conventional banding and molecular cytogenetics data of a 6-month-old boy with an AML-M5 presenting with a unique cryptic rearrangement involving the MLL gene: a three-way t(9;19;11)(p11.2;p13.1;q23).
Assuntos
Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 19/genética , Cromossomos Humanos Par 9/genética , Leucemia Mieloide Aguda/genética , Proteína de Leucina Linfoide-Mieloide/genética , Translocação Genética/genética , Humanos , Hibridização in Situ Fluorescente , Lactente , Cariotipagem , MasculinoRESUMO
The acute myeloid leukemia (AML) subtype M4Eo occurs in 5% of all AML cases and is usually associated with either an inv(16)(p13.1q22) or a t(16;16)(p13.1;q22) chromosomal abnormality. At the molecular level, these abnormalities generate a CBFB-MYH11 fusion gene. Patients with this genetic alteration are usually assigned to a low-risk group and thus receive standard chemotherapy. AML-M4Eo is rarely found in infants. We describe clinical, conventional banding, and molecular cytogenetic data for a 12-month-old baby with AML-M4Eo and a chimeric CBFB-MYH11 fusion gene masked by a novel rearrangement between chromosomes 1 and 16. This rearrangement characterizes a new type of inv(16)(p13.1q22) masked by a chromosome translocation.
Assuntos
Cromossomos Humanos Par 16 , Cromossomos Humanos Par 1 , Leucemia Mielomonocítica Aguda/genética , Proteínas de Fusão Oncogênica , Translocação Genética , Bandeamento Cromossômico , Humanos , Hibridização in Situ Fluorescente , Lactente , Cariotipagem , MasculinoRESUMO
In more than 90% of acute promyelocytic leukemia (APL) cases a reciprocal translocation t(15;17)(q22;q12) can be observed. The RARalpha gene on 17q12 is known to have other translocation partners than PML (in 15q22) in a minority of APL cases. Here, we describe a previously unrecorded chromosomal translocation involving the RARalpha gene and an unknown partner on chromosome 3. The chromosomal rearrangement was studied in detail by 24-color-FISH using whole chromosome painting probes plus multicolor banding. Thus, the breakpoint could be characterized as t(3;17) (q26;q12). In this case 10% of blasts showed AML-M3 characteristics although typical rearrangements with RARalpha were not detected by molecular methods. The characterization of the present and other comparable APL-cases with exceptional translocation partners of PML or RARalpha will help to enlighten the understanding of the pathogenesis of APL.