RESUMO
A syndrome akin to graft-versus-host disease in the recipient of syngeneic stem cells is hitherto described as being milder, self-limiting and confined to the skin. It is enhanced by prior cyclosporin A therapy. We describe here a recipient of a syngeneic marrow transplant who did not receive priming with cyclosporin A and yet developed severe and progressive graft-versus-host disease which necessitated and responded to high-dose immunosuppressive therapy. We believe that this is because the conditioning regimen in stem cell transplant acts to reset the immune system enabling it to recognise 'self' antigens. Bone Marrow Transplantation (2000) 25, 205-207.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Ciclosporina/administração & dosagem , Doença Enxerto-Hospedeiro/etiologia , Leucemia Mieloide Aguda/terapia , Condicionamento Pré-Transplante/efeitos adversos , Doença Aguda , Adolescente , Transplante de Medula Óssea/imunologia , Ciclosporina/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/patologia , Teste de Histocompatibilidade , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , MasculinoRESUMO
The Philadelphia chromosome is present in a heterogeneous group of leukemias. It is most commonly associated with chronic myelogenous leukemia (CML) and B-lineage acute lymphoblastic leukemia (ALL) being found in more than 95% and 15-25% of cases respectively. We undertook a study to determine the morphologic, phenotypic and molecular diversity of Philadelphia positive de novo acute leukemia patients seen at our institution over the past 3 1/2 years. Twenty-one patients with de novo acute leukemia were found to have the Philadelphia chromosome by cytogenetic studies. They consisted of 3 patients with acute myelogenous leukemia (AML), 1 biphenotypic leukemia and 17 ALL patients. Of the patients with ALL, 16 were of B-lineage while 1 had a T-cell phenotype. Ten patients expressed the p210 BCR-ABL transcript alone and 10 expressed only the p190 BCR-ABL transcript. One patient had co-expression of p190 and p210 b3a2 BCR-ABL transcripts. Thus the Philadelphia chromosome can be found in a diverse cohort of morphologic and immunologic subtypes of de novo acute leukemia reflecting the heterogeneity of lineage involvement in this disease.
Assuntos
Biomarcadores Tumorais/genética , Proteínas de Fusão bcr-abl/genética , Leucemia Mieloide/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Isoformas de Proteínas/genética , Doença Aguda , Adolescente , Adulto , Idoso , Antígenos CD/análise , Antígenos de Neoplasias/análise , Biomarcadores Tumorais/análise , Bandeamento Cromossômico , Feminino , Proteínas de Fusão bcr-abl/análise , Humanos , Imunofenotipagem , Leucemia Mieloide/patologia , Leucemia-Linfoma de Células T do Adulto/genética , Leucemia-Linfoma de Células T do Adulto/patologia , Masculino , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/imunologia , Células-Tronco Neoplásicas/patologia , Fenótipo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Isoformas de Proteínas/análise , RNA Mensageiro/biossíntese , RNA Mensageiro/genéticaAssuntos
Cromossomos Humanos Par 19 , Proteínas de Fusão bcr-abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Adulto , Fusão Gênica Artificial , Feminino , Proteínas de Fusão bcr-abl/biossíntese , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mieloide de Fase Crônica/genética , Leucemia Mieloide de Fase Crônica/metabolismo , Leucemia Mieloide de Fase Crônica/patologia , Reação em Cadeia da Polimerase , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transcrição GênicaRESUMO
We have cloned and sequenced the teleost homologs of the human genes encoding platelet-derived growth factor receptor-beta (PDGFR beta) and macrophage colony-stimulating factor 1 receptor (CSFIR) from the puffer fish Fugu rubripes. The Fugu PDGFR beta and CSFIR genes each consist of 21 coding exons similar to the human CSFI gene, but are considerably smaller than their human counterparts because of the smaller introns. Furthermore, the two Fugu genes are linked tandemly in a head-to-tail array similar to their human homologs with 2.2 kb of intergenic sequence. Amino acid sequences of the Fugu and human PDGFR beta and CSFIR genes show an overall homology of 45% and 39%, respectively, with the kinase domains showing a much higher degree of conservation. Dot-matrix analysis revealed several short stretches of conserved sequences in the 3' untranslated regions of the PDGFR beta genes and the adjacent promoter regions of the CSFIR genes. These conserved sequences may have a role in the regulation of expression of either or both of these closely linked genes.
Assuntos
Sequência Conservada , Peixes Venenosos/genética , Ligação Genética , Fator Estimulador de Colônias de Macrófagos/genética , Receptores do Fator de Crescimento Derivado de Plaquetas/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , DNA , Genes , Humanos , Dados de Sequência Molecular , Homologia de Sequência de AminoácidosRESUMO
We have identified novel BCR-ABL mRNA fusions by RT-PCR in two patients with Philadelphia (Ph) chromosome positive leukaemia. Sequencing revealed in-frame fusions consisting of part of BCR exon e8 spliced to ABL exon a2 in one patient and part of BCR exon e13 spliced to ABL exon a2 in the other. The breaks within BCR exons e8 and e13 did not conform to consensus splice sites, suggesting that the aberrant fusion mRNAs may have arisen as a result of translocation breakpoints at these sites. This was confirmed by genomic DNA bubble PCR for the second patient. These data show that BCR-ABL translocation breakpoints can occasionally occur within coding exons.