RESUMO
Acute myeloid leukemia (AML) is a heterogenous group of diseases affecting ~500 children in the United States annually. With current therapy, 90% of these children will obtain complete remission. However, 30% to 40% of these patients will relapse, most commonly within the first 3 years. Very late relapses, defined as relapse occurring >5 years after complete remission, are rare, accounting for 1% to 3% of relapses. We describe a patient with AML harboring an AFDN/KMT2A translocation who relapsed 12 years after matched sibling stem cell transplant, provide a brief review of the relevant literature, and describe proposed mechanisms to explain very late relapse AML.
Assuntos
Leucemia Mieloide Aguda/terapia , Adulto , Criança , Transplante de Células-Tronco Hematopoéticas , Histona-Lisina N-Metiltransferase/genética , Humanos , Cinesinas/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Proteína de Leucina Linfoide-Mieloide/genética , Miosinas/genética , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/genética , Translocação GenéticaAssuntos
Corpos Estranhos/diagnóstico por imagem , Migração de Corpo Estranho/diagnóstico por imagem , Linfadenopatia/diagnóstico por imagem , Pescoço , Pré-Escolar , Doença Crônica , Diagnóstico Diferencial , Ingestão de Alimentos , Corpos Estranhos/diagnóstico , Corpos Estranhos/cirurgia , Migração de Corpo Estranho/diagnóstico , Migração de Corpo Estranho/cirurgia , Humanos , Linfadenopatia/diagnóstico , Masculino , Radiografia Torácica/métodos , Medição de Risco , Resultado do Tratamento , Ultrassonografia Doppler/métodosRESUMO
A three-year-old boy presented with an enlarging neck mass. Biopsy demonstrated IgD-positive nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), which was staged as IIa. The patient received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) with rituximab and had excellent results. NLPHL is a relatively rare disease that is biologically distinct from classic Hodgkin lymphoma (cHL). NLPHL is a B-cell malignancy likely of germinal center origin that has an overall good prognosis and favorable response to treatment. Unlike cHL, NLPHL is ubiquitously CD20-positive. Recent evidence supports the efficacy of targeted anti-CD20 therapy in NLPHL, though prospective data is limited. This case demonstrates several unique features of NLPHL and further supports the use of rituximab in front-line therapy. The clinical characteristics among patients at various ages are discussed with a special focus on the IgD-positive subtype. A thorough literature search demonstrates this to be the youngest patient with NLPHL yet described.
RESUMO
Here we demonstrate that Arp2/3 regulates a transition between mesenchymal and amoeboid protrusions in MCF10A epithelial cells. Using genetic and pharmacological means, we first show Arp2/3 inhibition impairs directed cell migration. Arp2/3 inhibition results in a dramatically impaired cell adhesion, causing deficient cell attachment and spreading to ECM as well as an 8-fold decrease in nascent adhesion assembly at the leading edge. While Arp2/3 does not play a significant role in myosin-dependent adhesion growth, mature focal adhesions undergo large scale movements against the ECM suggesting reduced coupling to the ECM. Cell edge protrusions occur at similar rates when Arp2/3 is inhibited but their morphology is dramatically altered. Persistent lamellipodia are abrogated and we observe a markedly increased incidence of blebbing and unstable pseuodopods. Micropipette-aspiration assays indicate that Arp2/3-inhibited cells have a weak coupling between the cell cortex and the plasma membrane, and suggest a potential mechanism for increased pseudopod and bleb formation. Pseudopods are not sensitive to reduced in formin or myosin II activity. Collectively, these results indicate that Arp2/3 is not necessary for rapid protrusion of the cell edge but plays a crucial role in assembling focal adhesions required for its stabilization.
