Assuntos
Cromossomos Humanos Par 2 , Cromossomos Humanos Par 8 , Chaperonas Moleculares/genética , Doenças Mieloproliferativas-Mielodisplásicas/genética , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Translocação Genética , Feminino , Humanos , Pessoa de Meia-IdadeAssuntos
Linfócitos B/patologia , Interleucina-2/farmacologia , Cariotipagem/métodos , Ativação Linfocitária/efeitos dos fármacos , Transtornos Linfoproliferativos/patologia , Mitógenos/farmacologia , Oligonucleotídeos/farmacologia , Divisão Celular/efeitos dos fármacos , Células Cultivadas/efeitos dos fármacos , Células Cultivadas/ultraestrutura , Aberrações Cromossômicas , Bandeamento Cromossômico/métodos , Estudos de Coortes , Feminino , Humanos , Hibridização in Situ Fluorescente , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/patologia , Linfoma de Células B/genética , Linfoma de Células B/patologia , Transtornos Linfoproliferativos/genética , Masculino , Metáfase , Acetato de Tetradecanoilforbol/farmacologiaRESUMO
Thirty cases of acute myeloid leukaemia (AML) with MYST histone acetyltransferase 3 (MYST3) rearrangement were collected in a retrospective study from 14 centres in France and Belgium. The mean age at diagnosis was 59.4 years and 67% of the patients were females. Most cases (77%) were secondary to solid cancer (57%), haematological malignancy (35%) or both (8%), and appeared 25 months after the primary disease. Clinically, cutaneous localization and disseminated intravascular coagulation were present in 30 and 40% of the cases, respectively. AMLs were myelomonocytic (7%) or monocytic (93%), with erythrophagocytosis (75%) and cytoplasmic vacuoles (75%). Immunophenotype showed no particularity compared with monocytic leukaemia without MYST3 abnormality. Twenty-eight cases carried t(8;16)(p11;p13) with MYST3-CREBBP fusion, one case carried a variant t(8;22)(p11;q13) and one case carried a t(8;19)(p11;q13). Type I (MYST3 exon 16-CREBBP exon 3) was the most frequent MYST3-CREBBP fusion transcript (65%). MYST3 rearrangement was associated with a poor prognosis, as 50% of patients deceased during the first 10 months. All those particular clinical, cytologic, cytogenetic, molecular and prognostic characteristics of AML with MYST3 rearrangement may have allowed an individualization into the World Health Organization classification.
Assuntos
Cromossomos Humanos Par 8 , Rearranjo Gênico , Histona Acetiltransferases/genética , Leucemia Mieloide Aguda/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Primers do DNA , Feminino , Humanos , Imunofenotipagem , Hibridização in Situ Fluorescente , Cariotipagem , Leucemia Mieloide Aguda/imunologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
A retrospective cytogenetic study of acute myeloid leukemias (AML) and myelodysplastic syndromes (MDS) was conducted by the Groupe Francophone de Cytogénétique Hématologique (GFCH) to evaluate the structural abnormalities of chromosome 5 associated with other chromosomal abnormalities, in particular of chromosome 7, in these pathologies. In all, 110 cases of AML/MDS were recruited based on the presence of chromosome 5 abnormalities under conventional cytogenetics and supplemented by a systematic fluorescence in situ hybridization study of chromosomes 5 and 7. The abnormalities of the long arm of chromosome 5 (5q) were deletions of various sizes and sometimes cryptic. The 5q abnormalities were associated with translocations in 54% of cases and were simple deletions in 46%. In 68% of cases, 5q deletions were associated with chromosome 7 abnormalities, and 90% of these presented a complex karyotype. Of the 110 patients, 28 had a hematopoietic disorder secondary to chemotherapy, radiotherapy, or both. Among 82 patients with de novo AML/MDS, 63 were older than 60 years. Chromosomal abnormalities often associated hypodiploidy and chromosome 5 and 7 abnormalities in complex karyotypes, features resembling those of secondary hemopathies. Systematic investigation of the exposure to mutagens and oncogenes is thus essential to specify the factors potentially involved in MDS/AML with 5q abnormalities.
Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 5 , Cromossomos Humanos Par 7 , Leucemia Mieloide/genética , Síndromes Mielodisplásicas/genética , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Deleção Cromossômica , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Neoplasias Induzidas por Radiação , Translocação GenéticaRESUMO
A cytological, immunophenotypical and cytogenetical study of 136 chronic B-cell proliferations (93 CLL, 43 B-cell lymphomas) was led in order to precise diagnosis and to characterize and appreciate chromosomal rearrangements. In this series, mainly selected on blood lymphocytosis criteria, B-CLL were twice more frequent than small B-cell lymphomas. Probes used revealed cryptic abnormalities, which remained unknown by conventional cytogenetics (CC). The frequency of clonal abnormalities (CC and FISH) was 74.8% for this series, with 74.4% for lymphomas and 75.3% for CLL, mainly of Binet stage A (69 A, 13 B, 1 C, 10 unspecified). Proportion was 88.4% in A stages and 84.6% in B stages. In CLL, 13q14 cryptic deletions and translocations were widely majority, 14q32 translocations and trisomy 12 being predominant in lymphoma series. Interphase FISH study of non-clonal metaphasic abnormalities with locus-specific probes often revealed unrecognised clones.
Assuntos
Aberrações Cromossômicas , Cromossomos Humanos/genética , Leucemia Linfocítica Crônica de Células B/genética , Linfoma de Células B/genética , Aneuploidia , Cromossomos Humanos/ultraestrutura , Cromossomos Humanos Par 13/genética , Cromossomos Humanos Par 13/ultraestrutura , Células Clonais/patologia , Estudos de Coortes , Feminino , Humanos , Imunofenotipagem , Hibridização in Situ Fluorescente , Cariotipagem , Leucemia Linfocítica Crônica de Células B/patologia , Linfoma de Células B/patologia , Transtornos Linfoproliferativos/genética , Masculino , Estadiamento de Neoplasias , Deleção de SequênciaRESUMO
The assignment with chromosome banding techniques of the breakpoints of the recurrent translocation t(3;5) which leads to NPM1/MLF1 gene fusion in myeloid malignancies has not been unequivocal. In order to assess whether this is due to uncertainty in interpretation of the observed banding pattern or whether it reflects true genomic heterogeneity, we decided to analyze the breakpoint positions using fluorescence in situ (FISH) techniques in eight patients with myeloid malignancies and rearrangements of chromosomes 3 and 5. In three patients, colocalization of the NPM1 and MLF1 spanning BACs was demonstrated and NPM1/MLF1 fusion shown by PCR in one while in the remaining cases breakpoints were located outside the NPM1 and MLF1 loci. Interestingly, loss of a copy of the NPM1 gene was found in three of these latter patients. This findings suggest that haploinsufficiency of NPM1 may play a role in subtypes of myelodysplasias and leukemias.
Assuntos
Cromossomos Humanos Par 5/genética , Leucemia Mieloide/genética , Síndromes Mielodisplásicas/genética , Proteínas Nucleares/genética , Translocação Genética , Adulto , Idoso , Criança , Pré-Escolar , Bandeamento Cromossômico , Cromossomos Humanos Par 3/genética , Feminino , Hematopoese/genética , Humanos , Hibridização in Situ Fluorescente/métodos , Masculino , Nucleofosmina , Proteínas de Fusão Oncogênica/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Chromosomal abnormalities of erythroleukemia (EL) are often described as complex and unspecific. A retrospective study of 75 EL defined following the WHO classification was performed by the Groupe Francophone de Cytogénétique Hématologique (GFCH) in order to reexamine the cytogenetics of this infrequent leukemia subtype. Clonal chromosomal abnormalities were found in 57 patients (76%), distributed in 4 subgroups according to their ploidy status: pseudodiploid (16%), hypodiploid (47%), hyperdiploid (19%), and 18% mixed cases associating 2 different clones (hypodiploid+hyperdiploid) or (pseudodiploid+hyperdiploid). Complex rearrangements and hypodiploid chromosome number were widely dominant (50%). Partial or entire monosomies represented 56% of abnormalities. Chromosomes 5 and 7 were the most frequently involved (41 and 33 times, respectively), followed by chromosomes 8, 16, and 21 (19 times each). Unbalanced abnormalities were more frequent than balanced. All these kinds of abnormalities were observed in de novo as well as in secondary EL. Four out of 7 cases of "pure erythroid" leukemia were associated with a BCR-ABL fusion. Lastly, no chromosome abnormality specific to EL could be established. However, the large overlap of chromosomal abnormality patterns of EL (pure erythroid form excepted) and refractory anemia with excess of blasts in transformation (RAEB-t) favors the hypothesis of similarities between these 2 hematologic disorders.
Assuntos
Aberrações Cromossômicas , Leucemia Eritroblástica Aguda/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Cromossomos Humanos , Humanos , Pessoa de Meia-Idade , Ploidias , Estudos Retrospectivos , Análise de SobrevidaAssuntos
Fusão Gênica Artificial , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 9 , Proteínas de Homeodomínio/genética , Leucemia Mieloide/genética , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Translocação Genética , Doença Aguda , Sequência de Aminoácidos , Sequência de Bases , DNA de Neoplasias , Humanos , Cariotipagem , Leucemia Mieloide/etiologia , Dados de Sequência MolecularAssuntos
Proteínas de Ligação a DNA/genética , Amplificação de Genes/fisiologia , Síndromes Mielodisplásicas/genética , Proteínas Repressoras/genética , Idoso , Crise Blástica , Aberrações Cromossômicas , Análise Citogenética , Humanos , Masculino , Síndromes Mielodisplásicas/etiologia , Síndromes Mielodisplásicas/patologia , Proteínas Proto-Oncogênicas c-ets , Variante 6 da Proteína do Fator de Translocação ETSRESUMO
To accurately estimate the incidence of HOX11L2 expression, and determine the associated cytogenetic features, in T-cell acute lymphoblastic leukemia (T-ALL), the Groupe Français de Cytogénétique Hématologique (GFCH) carried out a retrospective study of both childhood and adult patients. In total, 364 patients were included (211 children
Assuntos
Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 5/genética , Proteínas de Homeodomínio/genética , Leucemia-Linfoma de Células T do Adulto/genética , Proteínas Oncogênicas/genética , Translocação Genética , Adolescente , Adulto , Criança , Pré-Escolar , Aberrações Cromossômicas , Células Clonais , Feminino , Humanos , Imunofenotipagem , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Ploidias , Proteínas Proto-Oncogênicas , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de SobrevidaRESUMO
The orphan homeobox gene HOX11L2 was previously found to be transcriptionally activated as a result of the t(5;14)(q35;q32) translocation in three T-ALL cases. We now tested by RT-PCR Hox11L2 expression in 23 consecutive cases of T-ALL (15 children aged 0.8-14 years, eight adults aged 17-55 years) and as control 13 B-ALL patients from a single institution. Hox11L2 expression was undetectable in all patients with B-ALL, nor in adults with T-ALL. Nine children (60% of the cases), all boys, expressed Hox11L2. Blast cells from most of the latter patients carried surface CD1a, CD10 and not CD34 antigens, in contrast to the other children. FISH, M-FISH and IPM-FISH analysis failed to detect a t(5;14)(q35;q32) in one of them, which suggests a possible distinct genetic mechanism in Hox11L2 expression induction. Hence, Hox11L2 expression seems to be the most frequent abnormality in childhood T-ALL to date, comparable to the t(12;21) in child B-ALL.
Assuntos
Proteínas de Homeodomínio/genética , Leucemia-Linfoma de Células T do Adulto/genética , Proteínas Oncogênicas/genética , Adolescente , Adulto , Fatores Etários , Idoso , Antígenos CD/análise , Estudos de Casos e Controles , Criança , Pré-Escolar , Cromossomos Humanos Par 14 , Cromossomos Humanos Par 5 , Feminino , Regulação da Expressão Gênica , Humanos , Imunofenotipagem , Incidência , Lactente , Leucemia-Linfoma de Células T do Adulto/mortalidade , Masculino , Proteínas Proto-Oncogênicas , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sobrevida , Taxa de Sobrevida , Translocação GenéticaRESUMO
We report three cases of T-ALL in which conventional cytogenetic analysis yielded normal karyotypes, but for which a new M-FISH technique (IPM-FISH) was able to detect a translocation. For these patients this technique highlighted a new, recurring and cryptic translocation t(5;14)(q35;q32) in childhood T-ALL which might be phenotypically restricted. The most innovative part of this technique is the use of interspersed polymerase chain reaction (IRS-PCR) painting probes that show an R-band pattern simultaneous with the combinatorial labeling. Contrary to the DOP-PCR, IRS-PCR-derived probes provide stronger hybridization signals at the telomeric ends that potentially increase the possibility of detecting cryptic translocations. All the IPM-FISH findings were validated by FISH with whole chromosome painting and unique sequence probes. These results demonstrate the efficient use of IPM-FISH as an improved, single-step method for the identification of cryptic chromosomal abnormalities. This new IPM-FISH technique is a good tool to display cryptic chromosomal abnormalities.