RESUMO
A child with acute pre-B cell lymphoblastic leukemia underwent haploidentical bone marrow transplantation (BMT) after first relapse. Approximately 8 months after the BMT, he developed a soft tissue mass overlying a defect in the left frontal bone. He was found to have several additional osteolytic lesions but no evidence of lymphadenopathy or organomegaly. A biopsy of the presenting lesion demonstrated a polymorphous infiltrate composed predominantly of S-100 protein and CD68 immunoreactive histiocytic cells. Together with the presence of emperipolesis, the process was interpreted as Rosai-Dorfman (R-D) disease. He received chemotherapy with vinblastine, prednisone, 6-mercaptopurine and methotrexate and has been in remission for over 4 years. Only one previous example of acute lymphoblastic leukemia in childhood has been reported with R-D disease.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Histiocitose Sinusal/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Adolescente , Antígenos CD , Antígenos de Diferenciação Mielomonocítica , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Evolução Fatal , Histiócitos , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Indução de Remissão , Proteínas S100RESUMO
A newborn baby boy was diagnosed with the mixed form of congenital mesoblastic nephroma (CMN) representing both classic and cellular histology features in the renal tumor. Additionally, the patient had skin and bone lesions consistent with multifocal involvement of a generalized infantile fibromatosis (IFS). Both skin and bone lesions were distinctly different from CMN and did not represent metastasis. The primary tumor cell line (MCH-MN-1), established from the resected right kidney tumor, had a diploid DNA content. Cytogenetic studies revealed deletion on the long arm of chromosome 3 (q21q24) and duplication on the short arm of chromosome 11 (p15). MCH-MN-1 cells expressed ETV6-NTRK3 gene fusion transcripts, characteristic of cellular and mixed forms of CMNs. The cells had high p21 and low Bax mRNA expression in the reverse transcriptase-polymerase chain reaction (RT-PCR) assay. The high level of proliferative marker (Ki67) mRNA expression correlated well with the pluripotent nature of MCH-MN-1 in tissue culture (cell doubling time = 12.4 h). Our results showed that MCH-MN-1 might be a good model cell line for investigations on mesoblastic nephroma.
Assuntos
Neoplasias Renais , Neoplasias Renais/congênito , Nefroma Mesoblástico , Deleção Cromossômica , Primers do DNA/química , DNA de Neoplasias/análise , Fibroma/complicações , Fibroma/congênito , Fibroma/genética , Fibroma/patologia , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica , Marcadores Genéticos/genética , Humanos , Recém-Nascido , Cariotipagem , Neoplasias Renais/complicações , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Nefroma Mesoblástico/complicações , Nefroma Mesoblástico/congênito , Nefroma Mesoblástico/genética , Nefroma Mesoblástico/patologia , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas/fisiologiaRESUMO
We have cloned the genomic breakpoints for a balanced t(14;21)(q11. 2;q22) chromosomal translocation associated with T-cell acute lymphoblastic leukemia. Sequence analysis of the genomic breakpoints indicated that the translocation had been mediated by an illegitimate V(D)J recombination event that disrupted the T-cell receptor (TCR) alpha locus and placed the TCR alpha locus enhancer on the derivative 21 chromosome. We identified a previously unreported transcript, designated BHLHB1 (for basic domain, helix-loop-helix protein, class B, 1) that had been activated by the translocation. BHLHB1 mapped to the region of chromosome 21 that has been proposed to be responsible, at least in part, for the learning deficits seen in children with Down's syndrome. Although BHLHB1 expression normally is restricted to neural tissues, T-cell lymphoblasts with the t(14;21)(q11.2;q22) also expressed high levels of BHLHB1 mRNA. Expression of BHLHB1 dramatically inhibited E2A-mediated transcription activation in NIH 3T3 fibroblasts and Jurkat T cells. This observation suggests that BHLHB1, similar to SCL/TAL1, may exert a leukemogenic effect through a functional inactivation of E2A or related proteins.
Assuntos
Cromossomos Humanos , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica , Leucemia-Linfoma de Células T do Adulto/genética , Fatores de Transcrição/genética , Translocação Genética , Sequência de Aminoácidos , Sequência de Bases , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Criança , Feminino , Rearranjo Gênico da Cadeia alfa dos Receptores de Antígenos dos Linfócitos T , Humanos , Dados de Sequência Molecular , Homologia de Sequência de Aminoácidos , Homologia de Sequência do Ácido NucleicoRESUMO
The expression of genes associated with apoptosis, cell proliferation and drug resistance in tumor cells was investigated in two pediatric Wilms' tumor patients (MCH-WT-1 and MCH-WT-3) for their association with cell cycle, daunorubicin accumulation and clinical data. DNA content, cell cycle and drug accumulation were analyzed immediately after surgery by flow cytometry and mRNA expression by reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Primary cell cultures were established from tumor specimens and tumor cells in both cases showed epithelial morphology. Although cell proliferation markers (Ki67 and PCNA) were expressed in both cases, MCH-WT-3 showed higher levels of mRNA expression, which corresponded, with metastatic behavior of the tumor in the patient. While p53 and p21 mRNAs were expressed at low levels in MCH-WT1, MCH-WT-3 showed high levels of p21 mRNA only. The increased expression of cyclin kinase inhibitor (p21) in MCH-WT-3 compared to MCH-WT-1 correlated with a higher percentage of G0/G1 cell population in the tumor specimen. Despite the expression of multidrug resistance markers (MDR1 and LRP) in MCH-WT-1, flow cytometric analysis showed tumor cell populations with very low and high daunorubicin accumulation and with the absence of any effect for verapamil and dipyridamole on daunorubicin accumulation of tumor cells.