RESUMO
Extramedullary infiltration (EMI), as a concomitant symptom of acute myeloid leukemia (AML), is associated with low complete remission and poor prognosis in AML. However, the mechanism of EMI remains indistinct. Clinical trials showed that increased miR-29s were associated with a poor overall survival in AML [14]. Nevertheless, they were proved to work as tumor suppressor genes by encouraging apoptosis and inhibiting proliferation in vitro. These contradictory results led us to the hypothesis that miR-29s may play a notable role in the prognosis of AML rather than leukemogenesis. Thus, we explored the specimens of AML patients and addressed this issue into miR-29c&b2 knockout mice. As a result, a poor overall survival and invasive blast cells were observed in high miR-29c&b2-expression patients, and the wildtype mice presented a shorter survival with heavier leukemia infiltration in extramedullary organs. Subsequently, we found that the miR-29c&b2 inside leukemia cells promoted EMI, but not the one in the microenvironment. The analysis of signal pathway revealed that miR-29c&b2 could target HMG-box transcription factor 1 (Hbp1) directly, then reduced Hbp1 bound to the promoter of non-muscle myosin IIB (Myh10) as a transcript inhibitor. Thus, increased Myh10 encouraged the migration of leukemia cells. Accordingly, AML patients with EMI were confirmed to have high miR-29c&b2 and MYH10 with low HBP1. Therefore, we identify that miR-29c&b2 contribute to the poor prognosis of AML patients by promoting EMI, and related genes analyses are prospectively feasible in assessment of AML outcome.
Assuntos
Leucemia Mieloide Aguda/genética , Infiltração Leucêmica/genética , Adulto , Idoso , Animais , Linhagem Celular Tumoral , Biologia Computacional/métodos , Bases de Dados Genéticas , Modelos Animais de Doenças , Feminino , Proteínas de Grupo de Alta Mobilidade/metabolismo , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Infiltração Leucêmica/metabolismo , Infiltração Leucêmica/patologia , Masculino , Camundongos , Camundongos Knockout , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Cadeias Pesadas de Miosina/metabolismo , Miosina não Muscular Tipo IIB/metabolismo , Prognóstico , Proteínas Repressoras/metabolismo , Taxa de Sobrevida , Adulto JovemRESUMO
We report a case of differentiation syndrome in a patient receiving the IDH1 inhibitor ivosidenib, with skin biopsy showing isocitrate dehydrogenase (IDH) R132H-mutated leukemia cutis. A 72-year-old man with IDH1-mutated acute myeloid leukemia (AML), status-post allogeneic cell transplantation, on ivosidenib for 6 months, was admitted for culture-negative neutropenic fever, pink and purpuric plaques and patches on the legs, abdomen and back, edema, hypotension, and shortness of breath. Skin biopsy revealed an infiltrate of atypical, immature, myeloperoxidase-positive mononuclear cells compatible with leukemia cutis or Sweet syndrome. Although dermal edema and interstitial neutrophilic infiltrate with karyorrhexis characteristic of Sweet syndrome were not seen, the atypical cells lacked expression of CD117 and CD34, which were expressed in the original leukemia. Additional immunohistochemical staining of suspected blasts was strongly positive for IDH1 R132H, suggesting a diagnosis of leukemia cutis. As the immunophenotype of blasts in skin infiltrates can significantly differ from the immunophenotype seen in blood and bone marrow, this case shows that mutation-specific antibodies such as anti-IDH1 R132H may be useful to help distinguish malignant from non-malignant infiltrates in the skin. Furthermore, differentiation syndrome may show histopathologic features of leukemia cutis on skin biopsy.
Assuntos
Antineoplásicos/uso terapêutico , Glicina/análogos & derivados , Isocitrato Desidrogenase/genética , Infiltração Leucêmica/patologia , Piridinas/uso terapêutico , Pele/patologia , Idoso , Diagnóstico Diferencial , Glicina/uso terapêutico , Humanos , Imuno-Histoquímica , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Infiltração Leucêmica/diagnóstico , Infiltração Leucêmica/genética , Masculino , Mutação , SíndromeAssuntos
Meato Acústico Externo/patologia , Hibridização in Situ Fluorescente , Leucemia Promielocítica Aguda/genética , Proteínas de Fusão Oncogênica/genética , Cariótipo Anormal , Antineoplásicos/uso terapêutico , Trióxido de Arsênio , Arsenicais/uso terapêutico , Terapia Combinada , Sondas de DNA , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/patologia , Leucemia Promielocítica Aguda/terapia , Infiltração Leucêmica/genética , Infiltração Leucêmica/patologia , Masculino , Pessoa de Meia-Idade , Óxidos/uso terapêutico , Tomografia por Emissão de Pósitrons , RNA Mensageiro/genética , RNA Neoplásico/genética , Recidiva , Tomografia Computadorizada por Raios X , Proteínas WT1/genéticaAssuntos
Técnicas Genéticas , Leucemia/diagnóstico , Linfoma/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Cariótipo Anormal , Exame de Medula Óssea , Aberrações Cromossômicas , Seguimentos , Humanos , Leucemia/genética , Leucemia/patologia , Infiltração Leucêmica/diagnóstico , Infiltração Leucêmica/genética , Linfoma/genética , Linfoma/patologia , Neoplasia Residual , Proteínas de Fusão Oncogênica/análise , Proteínas de Fusão Oncogênica/genética , Recidiva , Sensibilidade e EspecificidadeAssuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Infiltração Leucêmica/tratamento farmacológico , Idoso , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Infiltração Leucêmica/genética , Infiltração Leucêmica/patologia , MasculinoRESUMO
Cytopenias resulting from the impaired generation of normal blood cells from hematopoietic precursors are important contributors to morbidity and mortality in patients with leukemia. However, the process by which normal hematopoietic cells are overtaken by emerging leukemia cells and how different subsets of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) are distinctly influenced during leukemic cell infiltration is poorly understood. To investigate these important questions, we used a robust nonirradiated mouse model of human MLL-AF9 leukemia to examine the suppression of HSCs and HPCs during leukemia cell expansion in vivo. Among all the hematopoietic subsets, long-term repopulating HSCs were the least reduced, whereas megakaryocytic-erythroid progenitors were the most significantly suppressed. Notably, nearly all of the HSCs were forced into a noncycling state in leukemic marrow at late stages, but their reconstitution potential appeared to be intact upon transplantation into nonleukemic hosts. Gene expression profiling and further functional validation revealed that Egr3 was a strong limiting factor for the proliferative potential of HSCs. Therefore, this study provides not only a molecular basis for the more tightened quiescence of HSCs in leukemia, but also a novel approach for defining functional regulators of HSCs in disease.
Assuntos
Medula Óssea/patologia , Proteína 3 de Resposta de Crescimento Precoce/metabolismo , Células-Tronco Hematopoéticas/patologia , Leucemia Experimental/metabolismo , Leucemia Experimental/patologia , Infiltração Leucêmica/metabolismo , Infiltração Leucêmica/patologia , Animais , Proliferação de Células/fisiologia , Proteína 3 de Resposta de Crescimento Precoce/genética , Perfilação da Expressão Gênica , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Experimental/genética , Infiltração Leucêmica/genética , Camundongos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Neoplásico/genética , RNA Neoplásico/metabolismo , Fase de Repouso do Ciclo Celular , Baço/patologiaRESUMO
Mice repopulated with human hematopoietic cells are a powerful tool for the study of human hematopoiesis and immune function in vivo. However, existing humanized mouse models cannot support development of human innate immune cells, including myeloid cells and natural killer (NK) cells. Here we describe two mouse strains called MITRG and MISTRG, in which human versions of four genes encoding cytokines important for innate immune cell development are knocked into their respective mouse loci. The human cytokines support the development and function of monocytes, macrophages and NK cells derived from human fetal liver or adult CD34(+) progenitor cells injected into the mice. Human macrophages infiltrated a human tumor xenograft in MITRG and MISTRG mice in a manner resembling that observed in tumors obtained from human patients. This humanized mouse model may be used to model the human immune system in scenarios of health and pathology, and may enable evaluation of therapeutic candidates in an in vivo setting relevant to human physiology.
Assuntos
Imunidade Inata/genética , Imunidade Inata/imunologia , Células Matadoras Naturais , Células Mieloides , Animais , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/fisiologia , Infiltração Leucêmica/genética , Infiltração Leucêmica/imunologia , Camundongos , Camundongos Transgênicos , Células Mieloides/imunologia , Células Mieloides/fisiologia , Neoplasias Experimentais , Transplante HeterólogoAssuntos
Ascite/etiologia , Inversão Cromossômica , Cromossomos Humanos Par 16 , Leucemia Mielomonocítica Aguda/diagnóstico , Adulto , Ascite/patologia , Feminino , Humanos , Leucemia Mielomonocítica Aguda/complicações , Leucemia Mielomonocítica Aguda/genética , Leucemia Mielomonocítica Aguda/patologia , Infiltração Leucêmica/diagnóstico , Infiltração Leucêmica/genéticaRESUMO
Primary splenic small B-cell lymphomas mostly comprise the distinct entity of splenic marginal-zone lymphoma (SMZL) and the provisional category of splenic lymphoma/leukemia unclassifiable, mainly represented by the hairy cell leukemia variant and splenic diffuse red pulp small B-cell lymphoma (SDRL). Until recently, histopathologic examination of splenectomy specimens was considered mandatory for the diagnosis of SMZL. However, nowadays, mainly because of advances in chemoimmunotherapy, splenectomy is performed much less frequently. We evaluated the diagnostic efficacy of bone marrow biopsy (BMB) histopathology in the diagnostic approach toward SMZL and SDRL and tested whether it may serve as a substitute for spleen histopathology in the differential diagnosis between these 2 entities. To this end, we conducted a paired assessment of BMB and spleen diagnostic samples from 46 cases with a diagnosis of SMZL (n=32) or SDRL (n=14) based on spleen histopathology. We demonstrate that detailed immunohistopathologic BMB evaluation offers adequate evidence for the confirmation of these entities and their differential diagnosis from other small B-cell lymphoma histotypes. Notably, the immunophenotypical profile of SMZL and SDRL was identical in both BMB and spleen specimens for 21 evaluated markers. Paired assessment of BMB and spleen specimens did not identify discriminating patterns of BMB infiltration, cytology, and/or immunohistology between SMZL and SDRL. Accordingly, bone marrow histopathology contributes significantly in confirming the diagnosis of SMZL and SDRL. However, presently it is not possible to distinguish SMZL from SDRL on the basis of BMB evaluation alone; hence, histopathologic examination of the spleen remains the "gold standard" approach.
Assuntos
Células da Medula Óssea/patologia , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Baço/patologia , Neoplasias Esplênicas/diagnóstico , Adulto , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Células da Medula Óssea/metabolismo , DNA de Neoplasias/análise , Diagnóstico Diferencial , Feminino , Humanos , Infiltração Leucêmica/genética , Infiltração Leucêmica/metabolismo , Infiltração Leucêmica/patologia , Linfoma de Zona Marginal Tipo Células B/genética , Linfoma de Zona Marginal Tipo Células B/metabolismo , Masculino , Pessoa de Meia-Idade , Baço/metabolismo , Baço/cirurgia , Neoplasias Esplênicas/genética , Neoplasias Esplênicas/metabolismoAssuntos
Hibridização in Situ Fluorescente/métodos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Infiltração Leucêmica/genética , Infiltração Leucêmica/patologia , Adulto , Aberrações Cromossômicas , Feminino , Humanos , Leucemia Mieloide Aguda/terapia , Recidiva , Pele/patologiaRESUMO
Anaplastic large-cell lymphomas (ALCLs) bearing the t(2;5) translocation (ALK(+)ALCLs) are frequently characterized by skin colonization and associated with a poor prognosis. Using conditional transgenic models of anaplastic lymphoma kinase-positive (ALK(+)) lymphomas and human ALK(+)ALCL cell lines, in the present study, we show that high-mobility-group box-1 (HMGB-1), a proinflammatory cytokine, is released by ALK(+) cells, and demonstrate extracellular HMGB-1-stimulated secretion of the IL-8 chemokine by HaCaT keratinocytes through the involvement of MMP-9, PAR-2, and the NF-κB pathway. Furthermore, we demonstrate that, in vitro, IL-8 is able to induce the invasiveness of ALK(+) cells, which express the IL-8 receptors CXCR1 and CXCR2. In vitro and in vivo, HMGB-1 inhibition achieved by glycyrrhizin treatment led to a drastic reduction in ALK(+) cell invasiveness. The pathophysiological relevance of our observations was confirmed by demonstrating that the HMGB-1 and IL-8 receptors are expressed in ALK(+)ALCL biopsies. We have also shown that IL-8 secretion is correlated with leukemic dissemination of ALK(+) cells in a significant number of patients. The results of the present study demonstrate for the first time a relationship among the pro-inflammatory mediators HMGB-1, MMP-9, PAR-2, and IL-8. We propose that these mediators create a premetastatic niche within the skin, thereby participating in ALK(+) lymphoma epidermotropism.
Assuntos
Proteína HMGB1/fisiologia , Interleucina-8/metabolismo , Queratinócitos/metabolismo , Linfoma Anaplásico de Células Grandes/patologia , NF-kappa B/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Pele/metabolismo , Quinase do Linfoma Anaplásico , Animais , Células Cultivadas , Feminino , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Humanos , Queratinócitos/patologia , Infiltração Leucêmica/genética , Infiltração Leucêmica/metabolismo , Infiltração Leucêmica/patologia , Linfoma Anaplásico de Células Grandes/genética , Linfoma Anaplásico de Células Grandes/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos SCID , Camundongos Transgênicos , NF-kappa B/genética , Receptores Proteína Tirosina Quinases/genética , Receptor PAR-2/genética , Receptor PAR-2/metabolismo , Receptor PAR-2/fisiologia , Transdução de Sinais/fisiologia , Pele/patologia , Nicho de Células-Tronco/genética , Nicho de Células-Tronco/imunologiaRESUMO
Therapy-related acute leukemia showing mixed phenotype is extremely rare. We report a 49-year-old woman who presented with palpable masses in her neck and back. She had received systemic chemotherapy (adriamycin and cisplatin) and radiotherapy for endometrial adenocarcinoma 7 years before. Her peripheral blood and bone marrow showed increased blasts, which coexpressed myeloid (CD13, CD33, and myeloperoxidase) and B-lymphoid antigens (CD19 and CD79a). Cytogenetic analysis showed a karyotype of 46,XX,dup(1)(q21q32),add(5)(q33),t(9;22)(q34;q11.2)[12]/47,idem,+der(22)t(9;22)[8], and BCR/ABL1 rearrangement was detected. Leukemic infiltration was also confirmed in her back mass. After induction chemotherapy with idarubicin, cytarabine, and imatinib, she achieved complete remission. Only 2 cases of therapy-related acute leukemia with mixed phenotype have been reported so far: one with hyperploidy and the other with t(1;21)(p36;q22). To the best of our knowledge, this is the first case of therapy-related acute leukemia with mixed phenotype and t(9;22) as well as extramedullary leukemic infiltrations.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cromossomos Humanos Par 22/genética , Cromossomos Humanos Par 9/genética , Leucemia Mieloide Aguda/genética , Segunda Neoplasia Primária/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dorso , Benzamidas , Medula Óssea/patologia , Citarabina/administração & dosagem , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/radioterapia , Feminino , Rearranjo Gênico , Genes abl/genética , Humanos , Idarubicina/administração & dosagem , Mesilato de Imatinib , Imunofenotipagem , Quimioterapia de Indução , Cariotipagem , Leucemia Mieloide Aguda/induzido quimicamente , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Infiltração Leucêmica/induzido quimicamente , Infiltração Leucêmica/diagnóstico , Infiltração Leucêmica/genética , Infiltração Leucêmica/terapia , Pessoa de Meia-Idade , Segunda Neoplasia Primária/induzido quimicamente , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/terapia , Piperazinas/administração & dosagem , Pirimidinas/administração & dosagem , Indução de Remissão , Neoplasias de Tecidos Moles/induzido quimicamente , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/terapia , Neoplasias da Glândula Submandibular/induzido quimicamente , Neoplasias da Glândula Submandibular/diagnóstico , Neoplasias da Glândula Submandibular/genética , Neoplasias da Glândula Submandibular/terapia , Translocação GenéticaRESUMO
We explored the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and focal adhesion kinase (FAK) mRNA and protein, and analyzed the relationship between expression levels and clinical staging and extramedullary infiltration in patients with multiple myeloma (MM). The expression levels of mRNA and protein were measured by fluorescence quantitative polymerase chain reaction (FQ-PCR) and Western blotting. Expressions of PTEN and FAK mRNA were significantly different between patients with MM and controls. Spearman bivariate correlation analysis showed that PTEN mRNA was significantly negatively correlated with FAK mRNA. PTEN and FAK mRNA expressions were significantly different between patients with stage I + II MM and stage III MM. No difference was found in PTEN mRNA expression, whereas FAK mRNA expression was significantly different between patients with MM with and without extramedullary infiltration. PTEN protein was higher and total FAK (T-FAK) protein was significantly lower in six controls than in 12 patients with stage III MM. Phosphorylated FAK (p-FAK) protein was measured as 0.082 ± 0.040 in 11 patients with MM, but not detected in six controls. No significant difference of PTEN and T-FAK protein was found, while p-FAK protein was significantly different between patients with MM with and without extramedullary infiltration. These results indicate that abnormal expression of PTEN and FAK in patients with MM may be associated with disease progression and extramedullary infiltration.
Assuntos
Quinase 1 de Adesão Focal/genética , Infiltração Leucêmica/genética , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , PTEN Fosfo-Hidrolase/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/patologia , Estudos de Casos e Controles , Progressão da Doença , Feminino , Quinase 1 de Adesão Focal/metabolismo , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Infiltração Leucêmica/patologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Estadiamento de Neoplasias , PTEN Fosfo-Hidrolase/metabolismoRESUMO
BACKGROUND: Aleukaemic leukaemia--without blasts in the blood or the bone marrow--with isolated cutaneous manifestations has been very rarely reported since only seven patients have been described to date. The prognosis is variable, and the indications for an aggressive treatment such as polychemotherapy are currently unclear. We report a case of spontaneously remitting aleukaemic leukaemia in a newborn child and compare it with other cases in the literature. CASE REPORT: A male newborn presented diffuse, violaceous skin nodules reminiscent of the so-called "blueberry muffin syndrome" present since birth. Blood and marrow examinations did not show any blasts and karyotype was normal. Biopsy of a nodule established the diagnosis of acute myeloid leukaemia type 5. The course was spontaneously favourable despite the absence of specific therapy and the boy was asymptomatic after one year of follow-up. DISCUSSION: Of the eight reported infants (including ours), three died, including two through acute transformation of the leukaemia. The prognosis seems to be highly dependent on cytogenetic features with the 11q23 rearrangement being at higher risk of acute transformation, prompting recourse to aggressive chemotherapy. Our case further illustrates the favourable prognostic value of a normal karyotype, a situation in which therapeutic abstention seems possible, and is even recommended.
Assuntos
Leucemia Monocítica Aguda/congênito , Infiltração Leucêmica/congênito , Regressão Neoplásica Espontânea , Pele/patologia , Humanos , Imunofenotipagem , Recém-Nascido , Cariotipagem , Leucemia Monocítica Aguda/diagnóstico , Leucemia Monocítica Aguda/genética , Leucemia Monocítica Aguda/patologia , Infiltração Leucêmica/diagnóstico , Infiltração Leucêmica/genética , Infiltração Leucêmica/patologia , MasculinoRESUMO
Laminin α2 (LAMA2)-deficient congenital muscular dystrophy is a severe, early-onset disease caused by abnormal levels of laminin 211 in the basal lamina leading to muscle weakness, transient inflammation, muscle degeneration and impaired mobility. In a Lama2-deficient mouse model for this disease, animal survival is improved by muscle-specific expression of the apoptosis inhibitor Bcl-2, conferred by a MyoD-hBcl-2 transgene. Here we investigated early disease stages in this model to determine initial pathological events and effects of Bcl-2 on their progression. Using quantitative immunohistological and mRNA analyses we show that inflammation occurs very early in Lama2-deficient muscle, some aspects of which are reduced or delayed by the MyoD-hBcl-2 transgene. mRNAs for innate immune response regulators, including multiple Toll-like receptors (TLRs) and the inflammasome component NLRP3, are elevated in diseased muscle compared with age-matched controls expressing Lama2. MyoD-hBcl-2 inhibits induction of TLR4, TLR6, TLR7, TLR8 and TLR9 in Lama2-deficient muscle compared with non-transgenic controls, and leads to reduced infiltration of eosinophils, which are key death effector cells. This congenital disease model provides a new paradigm for investigating cell death mechanisms during early stages of pathogenesis, demonstrating that interactions exist between Bcl-2, a multifunctional regulator of cell survival, and the innate immune response.
Assuntos
Imunidade Inata/imunologia , Distrofia Muscular Animal/imunologia , Distrofia Muscular Animal/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Animais , Western Blotting , Imunidade Inata/genética , Marcação In Situ das Extremidades Cortadas , Infiltração Leucêmica/genética , Infiltração Leucêmica/imunologia , Infiltração Leucêmica/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Distrofia Muscular Animal/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Receptor 6 Toll-Like/genética , Receptor 6 Toll-Like/metabolismo , Receptor 7 Toll-Like/genética , Receptor 7 Toll-Like/metabolismo , Receptor 8 Toll-Like/genética , Receptor 8 Toll-Like/metabolismo , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/metabolismoRESUMO
Extramedullary (EM) manifestations of acute leukemia include a wide variety of clinically significant phenomena that often pose therapeutic dilemmas. Myeloid sarcoma (MS) and leukemia cutis (LC) represent 2 well-known EM manifestations with a range of clinical presentations. MS (also known as granulocytic sarcoma or chloroma) is a rare EM tumor of immature myeloid cells. LC specifically refers to the infiltration of the epidermis, dermis, or subcutis by neoplastic leukocytes (leukemia cells), resulting in clinically identifiable cutaneous lesions. The molecular mechanisms underlying EM involvement are not well defined, but recent immunophenotyping, cytogenetic, and molecular analysis are beginning to provide some understanding. Certain cytogenetic abnormalities are associated with increased risk of EM involvement, potentially through altering tissue-homing pathways. The prognostic significance of EM involvement is not fully understood. Therefore, it has been difficult to define the optimal treatment of patients with MS or LC. The timing of EM development at presentation versus relapse, involvement of the marrow, and AML risk classification help to determine our approach to treatment of EM disease.
Assuntos
Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Infiltração Leucêmica/patologia , Infiltração Leucêmica/terapia , Sarcoma Mieloide/patologia , Sarcoma Mieloide/terapia , Pele/patologia , Aberrações Cromossômicas , Tratamento Farmacológico , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/genética , Infiltração Leucêmica/complicações , Infiltração Leucêmica/genética , Mutação , Prognóstico , Sarcoma Mieloide/complicações , Sarcoma Mieloide/genéticaRESUMO
Hepatosplenic T-cell lymphoma (HSTL) represents a rare form of peripheral T-cell lymphoma composed of lymphocytes that typically express the γδ T-cell receptor. This form of lymphoma rarely involves the skin. We report the case of a 23-year-old man with a history of HSTL that was presumed to be in remission who presented with a solitary cutaneous nodule. Skin biopsy showed an atypical lymphocytic infiltrate arranged in a perivascular and periappendageal pattern with associated vacuolar epidermal interface change. The constituent T cells expressed CD2, CD3, CD7, CD8, ß-F1, γδ T-cell receptor, Tia-1 and granzyme B. The cells lacked the expression of CD4, CD5 and CD56. Fluorescence in situ hybridization (FISH) showed a characteristic chromosomal abnormality, namely isochromosome 7q, which confirmed the diagnosis of cutaneous HSTL. On restaging his disease, widespread progression was noted. To our knowledge, this report provides the first detailed account of cutaneous involvement by HSTL. We show the novel utility of FISH to identify isochromosome 7q in the lesional skin of HSTL patients.
Assuntos
Neoplasias Hepáticas/diagnóstico , Linfoma de Células T/diagnóstico , Neoplasias Cutâneas/diagnóstico , Neoplasias Esplênicas/diagnóstico , Aberrações Cromossômicas , Cromossomos Humanos Par 7 , DNA de Neoplasias/análise , Diagnóstico Diferencial , Progressão da Doença , Humanos , Hibridização in Situ Fluorescente , Infiltração Leucêmica/diagnóstico , Infiltração Leucêmica/genética , Infiltração Leucêmica/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Linfoma de Células T/genética , Linfoma de Células T/metabolismo , Masculino , Estadiamento de Neoplasias , Recidiva , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Neoplasias Esplênicas/genética , Neoplasias Esplênicas/metabolismo , Adulto JovemAssuntos
Leucemia Mieloide Aguda/complicações , Infiltração Leucêmica/genética , Derrame Pleural Maligno/etiologia , Aberrações Cromossômicas , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Derrame Pleural Maligno/genética , Derrame Pleural Maligno/terapiaRESUMO
OBJECTIVE: To investigate role of WASP family verprolin homologous protein 1 (WAVE1) in K562 leukemia cell invasion and its mechanism. METHODS: Immunofluorescence method was used to detect the distribution of WAVE1 and MMP-2 in the cells. K562 cells were transfected with pcDNA3. 1-WAVE1 reconstructed plasmid or with specific siRNA to WAVE1 gene. The invasion ability of K562 cells was examined by Transwell assay. The expression level of WAVE1 and MMP-2 in K562 cells was assayed by real-time PCR and Western blot. RESULTS: (1) WAVE1 and MMP-2 mainly expressed and co-localized in the cell membrane; (2) 24 h and 48 h after transfected with pcDNA3. 1-WAVE1, the MMP-2 mRNA level in K562 cells increased by 295% and 198% while its protein increased by 80% and 23% respectively as compared with control K562 cells. At the same time point after transfected with specific siRNA, the MMP-2 mRNA level decreased by 81% and 28%, and its protein decreased by 36% and 53% respectively as compared with control. (3) The invasion ability of K562 cells was enhanced after transfected with pcDNA3. 1-WAVE1 and depressed after transfected with the specific siRNA. CONCLUSION: The co-localization of WAVE1 and MMP-2 in K562 cells suggests they coordinate in functions; WAVE1 may involve in the migration and invasion of K562 cells through regulating the expression level of MMP-2.