RESUMO
BACKGROUND: Children with Down syndrome (DS) have an enhanced risk of developing acute leukemia, with the most common subtype being acute megakaryoblastic leukemia (AMKL). Myeloid leukemia in Down syndrome (ML-DS) is considered a disease with distinct clinical and biological features. There are few studies focusing on the clonal cytogenetic changes during evolution of ML-DS. CASE PRESENTATION: Here, we describe a complex karyotype involving a previously unreported set of chromosomal abnormalities acquired during progression of ML-DS in an infant boy: derivative der(1)t(1;15)(q24;q23), translocation t(4;5)(q26;q33) and derivative der(15)t(7;15)(p21;q23). Different molecular cytogenetic probes and probesets including whole chromosome painting (WCP) and locus specific probes, as well as, multicolor-FISH and multicolor chromosome banding (MCB) were performed in order to characterize the chromosomal abnormalities involved in this complex karyotype. The patient was treated according to the acute myeloid leukemia-Berlin-Frankfurt-Munich-2004 (AML-BFM 2004) treatment protocol for patients with Down syndrome; however, he experienced a poor clinical outcome. CONCLUSION: The molecular cytogenetic studies performed, allowed the characterization of novel chromosomal abnormalities in ML-DS and possible candidate genes involved in the leukemogenic process. Our findings suggest that the complex karyotype described here was associated with the poor prognosis.
RESUMO
Deletions in the long arm of chromosome 5 or loss of the whole chromosome are rare in childhood Acute Myeloid Leukemia (AML) patients. It is also unknown if the wide variety of breakpoints have diverging implications in the patient's outcome. Despite -5/5q- abnormalities have usually been described as a poor prognostic feature, however, the low frequency of -5/5q- in pediatric AML patients limits a full knowledge about this cytogenetic and clinical category, which is an intriguing factor for further research and new findings. Here, we report an AML child showing an uncommon deletion in 5q associated with 2 new abnormalities involving chromosome 2 within a complex karyotype well-characterized by several molecular cytogenetic approaches. Our work stimulates upcoming studies with more detailed descriptions about 5q abnormalities to better define its role in the stratification risk of such cytogenetic subgroup in childhood AML.
Assuntos
Cromossomos Humanos Par 11/genética , Amplificação de Genes , Proteína de Leucina Linfoide-Mieloide/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Trissomia , Adolescente , Bandeamento Cromossômico , Feminino , Histona-Lisina N-Metiltransferase , Humanos , Hibridização in Situ Fluorescente , CariótipoAssuntos
Cromossomos Humanos Par 9/ultraestrutura , Deleção de Genes , Genes p16 , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Translocação Genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzamidas/administração & dosagem , Criança , Cromossomos Humanos Par 9/genética , Evolução Clonal , Células Clonais/ultraestrutura , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Proteínas de Fusão bcr-abl/genética , Humanos , Mesilato de Imatinib , Cariótipo , Masculino , Células-Tronco Neoplásicas/ultraestrutura , Cromossomo Filadélfia , Piperazinas/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Pirimidinas/administração & dosagemAssuntos
Cromossomos Humanos Par 10/genética , Cromossomos Humanos Par 11/genética , Leucemia Monocítica Aguda/genética , Proteína de Leucina Linfoide-Mieloide/genética , Proteínas Recombinantes de Fusão/genética , Fatores de Transcrição/genética , Cariótipo Anormal , Sequência de Bases , Cromossomos Artificiais Bacterianos , Histona-Lisina N-Metiltransferase , Humanos , Lactente , Masculino , Dados de Sequência Molecular , Reação em Cadeia da Polimerase Via Transcriptase ReversaAssuntos
Cromossomos Humanos Par 21/genética , Cromossomos Humanos Par 8/genética , Leucemia Mieloide/genética , Translocação Genética , Doença Aguda , Criança , Bandeamento Cromossômico , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Variação Genética , Humanos , Cariotipagem , Leucemia Mieloide/diagnóstico , Leucemia Mieloide/tratamento farmacológico , Masculino , Proteínas de Fusão Oncogênica/genética , Proteína 1 Parceira de Translocação de RUNX1 , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Classical Burkitt lymphoma/leukemia (BL/L) presenting L3 morphology is found in 1% of childhood ALL. Recently, it has been described that secondary abnormalities could influence the prognosis of these patients. However, little information is available on these cytogenetic abnormalities and their prognostic importance in BL/L. Here, we report four new childhood BL/L cases associated with duplication within 1q or 13q, which exhibited a very unfavorable therapeutic response. We performed both classical and molecular cytogenetic analysis by multicolor chromosome banding of the secondary abnormalities involving the long arms of chromosome 1 or 13. These patients were previously treated with BFM-90 protocol. All of them died during or after the initial treatment. Here, for the first time, the exact breakpoints of the derivative chromosomes involved were determined at the cytogenetic level as 1q21 and 13q33 each.
Assuntos
Linfoma de Burkitt/genética , Cromossomos Humanos Par 13/genética , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 8/genética , Duplicação Gênica , Rearranjo Gênico , Linfoma de Burkitt/diagnóstico , Criança , Pré-Escolar , Pontos de Quebra do Cromossomo , Humanos , Masculino , Prognóstico , Índice de Gravidade de DoençaAssuntos
Crise Blástica/genética , Cromossomos Humanos/genética , Leucemia Mieloide Aguda/genética , Mutagênese Insercional , Translocação Genética , Crise Blástica/metabolismo , Regulação Leucêmica da Expressão Gênica , Histona-Lisina N-Metiltransferase , Humanos , Lactente , Leucemia Mieloide Aguda/metabolismo , Masculino , Proteína de Leucina Linfoide-Mieloide/biossíntese , Proteína de Leucina Linfoide-Mieloide/genética , Proteínas de Fusão Oncogênica/biossíntese , Proteínas de Fusão Oncogênica/genéticaRESUMO
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
BACKGROUND: Children with Down syndrome (DS) have an increased risk of childhood acute leukemia, especially acute megakaryoblastic leukemia (AMKL) also called acute myeloid leukemia (AML) type M7. Here four yet unreported infants with such malignancies are reported. RESULTS: An unbalanced translocation involving chromosome 1 was identified by GTG banding in all cases. These were characterized in more detail by molecular cytogenetic approaches. Additional molecular analysis revealed in three of the four cases mutations in exon 2 of the GATA binding protein 1 (globin transcription factor 1), located in Xp11.23. CONCLUSION: Our results corroborate that abnormalities of chromosome 1 are common in DS-associated AMKL. Whether this chromosomal region contains gene(s) involved in hematopoietic malignant transformation remains to be determined.
RESUMO
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.