RESUMO
Erythroblastic synartesis is a rare cause of acquired dyserythropoiesis. Only 9 cases have been previously reported. We hereby report 3 cases of patients diagnosed with erythroblastic synartesis associated with monoclonal immunoglobulin and an overt malignant lymphoid disorder. A different B-cell clone may produce the monoclonal immunoglobulin, forming a biclonal disorder. In light of these data and literature review, treatment targeting the paraprotein seems to be efficient to control synartesis and correct anemia. In the case of monoclonal gammapathy associated with chronic lymphocytic leukemia, therapeutics should be adapted to control both chronic lymphocytic leukemia and monitored monoclonal immunoglobulin titer.
Assuntos
Leucemia Linfocítica Crônica de Células B , Transtornos Linfoproliferativos , Paraproteinemias , Anticorpos Monoclonais , Eritroblastos/patologia , Humanos , Leucemia Linfocítica Crônica de Células B/patologia , Transtornos Linfoproliferativos/complicações , Paraproteinemias/complicaçõesRESUMO
Mutations in the MPL gene encoding the human thrombopoietin receptor (TpoR) drive sporadic and familial essential thrombocythemias (ETs). We identified 2 ET patients harboring double mutations in cis in MPL, namely, L498W-H499C and H499Y-S505N. Using biochemical and signaling assays along with partial saturation mutagenesis, we showed that L498W is an activating mutation potentiated by H499C and that H499C and H499Y enhance the activity of the canonical S505N mutation. L498W and H499C can activate a truncated TpoR mutant, which lacks the extracellular domain, indicating these mutations act on the transmembrane (TM) cytosolic domain. Using a protein complementation assay, we showed that L498W and H499C strongly drive dimerization of TpoR. Activation by tryptophan substitution is exquisitely specific for position 498. Using structure-guided mutagenesis, we identified upstream amino acid W491 as a key residue required for activation by L498W or canonical activating mutations such as S505N and W515K, as well as by eltrombopag. Structural data point to a common dimerization and activation path for TpoR via its TM domain that is shared between the small-molecule agonist eltrombopag and canonical and novel activating TpoR mutations that all depend on W491, a potentially accessible extracellular residue that could become a target for therapeutic intervention.
Assuntos
Benzoatos/farmacologia , Predisposição Genética para Doença , Hidrazinas/farmacologia , Mutação , Pirazóis/farmacologia , Receptores de Trombopoetina/agonistas , Receptores de Trombopoetina/genética , Trombocitemia Essencial/genética , Alelos , Substituição de Aminoácidos , Linhagem Celular , Estudos de Associação Genética , Humanos , Fenótipo , Transdução de Sinais/efeitos dos fármacos , Trombocitemia Essencial/diagnóstico , Trombocitemia Essencial/metabolismoAssuntos
Leucemia Mieloide Aguda/genética , Transtornos Mieloproliferativos/genética , Subunidade p45 do Fator de Transcrição NF-E2/genética , Adulto , Feminino , Humanos , Leucemia Mieloide Aguda/epidemiologia , Masculino , Pessoa de Meia-Idade , Mutação , Transtornos Mieloproliferativos/epidemiologia , Análise de SobrevidaRESUMO
Histological transformation (HT) to diffuse large B-cell lymphoma (DLBCL) is a rare and poorly reported complication of Waldenström macroglobulinaemia (WM). We performed a retrospective study of 77 WM patients with biopsy-proven transformation to DLBCL. The median time from WM diagnosis to HT was 4·6 years and 16 patients (21%) had never been treated for WM. At HT, extranodal sites were observed in 91% of patients with a rather high incidence of central nervous system, cutaneous or testicular involvement. Fluorodeoxyglucose-positron emission tomography was performed in half of the patients and the median maximum standardized uptake value was 15 for transformed disease. More than 80% of cases with available data for assessment by the Hans' algorithm harboured a non-germinal centre B-cell phenotype. First-line treatment for transformation consisted of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)-like regimen in 85% of patients. The overall response rate after first-line treatment was 61% and the median overall survival was only 16 months for the entire cohort. Time to transformation above 5 years (P = 0·0004) and elevated LDH (P = 0·02) were associated with worse outcome. Based on these findings, HT should be considered and lead to a biopsy in WM patients presenting with extranodal involvement, elevated LDH and constitutional symptoms. The optimal therapeutic approaches remain to be defined.
Assuntos
Transformação Celular Neoplásica/patologia , Linfoma Difuso de Grandes Células B/patologia , Macroglobulinemia de Waldenstrom/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Biópsia , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Fluordesoxiglucose F18 , Humanos , L-Lactato Desidrogenase/sangue , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Prednisona/uso terapêutico , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Rituximab , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Vincristina/uso terapêutico , Macroglobulinemia de Waldenstrom/diagnóstico por imagemAssuntos
Carioferinas/genética , Leucemia Linfocítica Crônica de Células B/epidemiologia , Leucemia Linfocítica Crônica de Células B/genética , Mutação , Receptores Citoplasmáticos e Nucleares/genética , Alelos , Biomarcadores Tumorais , Evolução Clonal , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/mortalidade , Prevalência , Prognóstico , Proteína Exportina 1RESUMO
The optimal management of patients with relapsed chronic lymphocytic leukemia (CLL) is dictated by the type of prior therapy, duration of prior response, presence of genomic aberrations, age, and comorbidities. The patterns of relapses and the clinical outcomes of second-line options after fludarabine-cyclophosphamide-rituximab (FCR) is given as a frontline treatment are currently unknown. In this retrospective and non-randomized study, we report the outcomes of 132 patients from databases of 14 French CLL study group centers who needed a second-line treatment after FCR frontline. Bendamustine + rituximab (BR) was the most frequently used second-line regimen, followed by alemtuzumab-based regimens, R-CHOP, and FCR. Median progression-free survival (PFS) was 18 months after BR with a median overall survival (OS) not reached. We also found that response durations of < 36 months and the presence of del(17p) are critical factors that contribute to poor overall survival. BR appears to be an effective salvage regimen in our series, both in terms of progression-free and overall survival. Patients who relapsed less than 36 months after FCR have a poor outcome, not significantly different in this study from patients with early relapses less than 12 or 24 months.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bases de Dados Factuais , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/mortalidade , Terapia de Salvação , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Deleção Cromossômica , Cromossomos Humanos Par 17/genética , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , França/epidemiologia , Humanos , Leucemia Linfocítica Crônica de Células B/genética , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Recidiva , Estudos Retrospectivos , Fatores de Risco , Rituximab , Taxa de Sobrevida , Fatores de Tempo , Vincristina/administração & dosagemRESUMO
Hairy cell leukaemia (HCL) is a rare haematological malignancy, with approximately 175 new incident cases in France. Diagnosis is based on a careful examination of the blood smear and immunophenotyping of the tumour cells, with a panel of four markers being used specifically to screen for hairy cells (CD11c, CD25, CD103 and CD123). In 2011, the V600E mutation of the BRAF gene in exon 15 was identified in HCL; being present in HCL, it is absent in the variant form of HCL (HCL-v) and in splenic red pulp lymphoma (SRPL), two entities related to HCL. The management of patients with HCL has changed in recent years. A poorer response to purine nucleoside analogues (PNAs) is observed in patients with more marked leukocytosis, bulky splenomegaly, an unmutated immunoglobulin variable heavy chain (IgVH) gene profile, use of VH4-34 or with TP53 mutations. We present the recommendations of a group of 11 experts belonging to a number of French hospitals. This group met in November 2013 to examine the criteria for managing patients with HCL. The ideas and proposals of the group are based on a critical analysis of the recommendations already published in the literature and on an analysis of the practices of clinical haematology departments with experience in managing these patients. The first-line treatment uses purine analogues: cladribine or pentostatin. The role of BRAF inhibitors, whether or not combined with MEK inhibitors, is discussed. The panel of French experts proposed recommendations to manage patients with HCL, which can be used in a daily practice.
Assuntos
Leucemia de Células Pilosas/diagnóstico , Leucemia de Células Pilosas/terapia , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/uso terapêutico , Antígenos CD/análise , Antígenos de Neoplasias/análise , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfócitos B/patologia , Biomarcadores Tumorais , Diagnóstico Diferencial , Éxons/genética , Feminino , Rearranjo Gênico de Cadeia Pesada de Linfócito B , Humanos , Imunofenotipagem , Interferon-alfa/administração & dosagem , Interferon-alfa/uso terapêutico , Leucemia de Células Pilosas/sangue , Leucemia de Células Pilosas/genética , Leucemia de Células Pilosas/patologia , Linfoma não Hodgkin/diagnóstico , Masculino , Mutação , Proteínas de Neoplasias/genética , Gravidez , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Prognóstico , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Rituximab , Terapia de Salvação , Neoplasias Esplênicas/diagnósticoAssuntos
Nefrite Intersticial , Macroglobulinemia de Waldenstrom , Idoso , Humanos , Masculino , Nefrite Intersticial/sangue , Nefrite Intersticial/diagnóstico , Nefrite Intersticial/patologia , Macroglobulinemia de Waldenstrom/sangue , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/patologiaAssuntos
Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Pneumonia/induzido quimicamente , Purinas/efeitos adversos , Quinazolinonas/efeitos adversos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Humanos , Pulmão/diagnóstico por imagem , Masculino , Purinas/administração & dosagem , Quinazolinonas/administração & dosagem , Rituximab/administração & dosagem , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Serine/threonine phosphatases are responsible for modulating the activities of the protein kinases implicated in the development of several pathologies. Here we identified by a PEP-scan approach a peptide of LRRK2, a Parkinson's disease associated protein, interacting with the phosphatase PP1. In order to study its biological activity, the peptide was fused via its N-terminal to an optimized cell penetrating peptide. We synthesized from the original peptide five interfering peptides and identified two (Mut3DPT-LRRK2-Short and Mut3DPT-LRRK2-Long) able to disrupt the LRRK2/PP1 interaction by competition in anti-LRRK2 immunoprecipitates. Using FITC-labelled peptides, we confirmed their internalization into cell lines as well as into primary cells obtained from healthy or ill human donors. We confirmed by ELISA test the association of Mut3DPT-LRRK2-Long peptide to purified PP1 protein. The peptides Mut3DPT-LRRK2-5 to 8 with either N or C-terminal deletions were not able to disrupt the association LRRK2/PP1 nor to associate with purified PP1 protein. The interfering sequences blocking the PP1/LRRK2 interaction were also fused to a shuttle peptide able to cross the blood brain barrier and showed that the newly generated peptides BBB-LRRK2-Short and BBB-LRRK2-Long were highly resistant to protease degradation. Furthermore, they blocked PP1/LRRK2 interaction and they penetrated into cells. Hence, these newly generated peptides can be employed as new tools in the investigation of the role of the LRRK2/PP1 interaction in normal and pathological conditions.
Assuntos
Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/metabolismo , Oligopeptídeos/química , Proteína Fosfatase 1/metabolismo , Sítios de Ligação , Linhagem Celular Tumoral , Células Cultivadas , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/química , Oligopeptídeos/síntese química , Oligopeptídeos/farmacologia , Ligação Proteica/efeitos dos fármacos , ProteóliseRESUMO
Cell penetrating peptides (CPP) are able cross the membrane and to transport cargos, presenting a great potential in drug delivery and diagnosis. In this paper, we have identified novel natural or synthetic CPPs. We have validated their rapid and efficient time and dose-dependent penetration, the absence of toxicity, the intracellular localization and the stability to proteases degradation, one of the main bottlenecks of peptides. Moreover, we have associate a cargo (an interfering peptide blocking the association of the serine/threonine phosphatase PP2A to its inhibitor, the oncogene SET) to the new generated shuttles and showed that they new bi-functional peptides keep the original properties of the shuttle and, in addition, are able to induce apoptosis due to the properties of the cargo. The CPPs identified in this study have promising perspectives for future anti-cancer drug delivery.
RESUMO
BACKGROUND: Reactivation of occult hepatitis B virus (HBV) infection is a well-known complication of cytotoxic chemotherapy. Lamivudine prophylaxis is recommended to reduce the incidence and severity of hepatitis in this context. CASE REPORT: An HIV-infected patient positive for HBs antigen became positive for HBc antibody alone under lamivudine given as part of antiretroviral therapy. He was treated with chemotherapy for non-Hodgkin's lymphoma while under lamivudine. Then, he developed HBV-related hepatitis that led to delay chemotherapy. He received adefovir that induced a dramatic decline in HBV DNA load and a normalisation of hepatic enzyme levels. However, the patient died of a relapse of lymphoma. Retrospective analysis of stored plasma samples showed evidence of lamivudine-resistant occult hepatitis before the onset of chemotherapy and reactivation of the HBV mutant. CONCLUSION: To our knowledge, this is the first report of occult hepatitis reactivation due to lamivudine-resistant mutant selected under lamivudine therapy in an HIV-infected patient. Our study underlines the need to carefully investigate lamivudine resistance in HIV-infected patients with occult infection under lamivudine therapy. Those patients should be monitored with the addition of anti-viral agents effective against the mutant strain.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Infecções por HIV/virologia , Vírus da Hepatite B/fisiologia , Hepatite B/virologia , Lamivudina/farmacologia , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/virologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Farmacorresistência Viral , HIV/efeitos dos fármacos , HIV/genética , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/genética , Humanos , Linfoma não Hodgkin/imunologia , Masculino , Ativação Viral/efeitos dos fármacosRESUMO
BACKGROUND: Disruption of alternative splicing in apoptotic factors has been associated to chronic lymphocytic leukemia among other cancers and hematological malignancies. The proapoptotic proteins Caspase-9 and PP2Acα are functionally related in a direct interaction, which constitutes a promising target for cancer therapy. Both proteins present aberrant mRNA splicing variants that are antiapoptotic (Caspase-9b) and catalytically inactive (PP2Acα2), respectively. RESULTS: In this work we have analyzed the relative abundance of the aberrant spliced forms Caspase-9b and PP2Acα2 in several cell lines and chronic lymphocytic leukemia patients and correlated it with several parameters of the disease. Despite 40 % of the patients presented Caspase-9b dysregulation, there was no direct association between alterations in Caspase-9b relative abundance and the parameters analyzed in medical records. More importantly, PP2Acα2 dysregulation was observed in 88 % of CLL patients and was related with advanced stages of the malignancy. CONCLUSIONS: Caspase-9b dysregulation seemed to be associated with the disease, although the differences between healthy donors and CLL patients were not statistically significant. However, PP2Acα2 dysregulation was significantly different between healthy donors and CLL patients and correlated with Binet B and C stages; therefore, we propose the use of PP2Acα2 dysregulation as a potential biomarker for advanced stages of chronic lymphocytic leukemia.
RESUMO
Acute hemorragic and thrombotic complications in cancer are often life threatening. Hemorragic disease are frequent (10%) and sometimes revealed the cancer. In more than 50% thrombocytopenia is involved. Bleeding is related to a vessel wound in 30% of the hemorragic complications either by a tumoral diffusion or by the tumor itself. In less than 10%, the bleeding is linked to disseminated intravascular coagulation. Very rarely coagulation factor deficit is found. Thrombotic manifestations are also frequent (15% of cancer patients). Venous system are usually involved. Clinicians must be aware of these complications to favor the best treatment early as possible to prevent fatal complications.
Assuntos
Hemorragia/etiologia , Hemorragia/terapia , Neoplasias/complicações , Trombose/etiologia , Trombose/terapia , Humanos , Fatores de RiscoAssuntos
Aspergilose/diagnóstico , Aspergilose/etiologia , Criptococose/diagnóstico , Criptococose/etiologia , Meningoencefalite/diagnóstico , Meningoencefalite/etiologia , Pirazóis/efeitos adversos , Pirimidinas/efeitos adversos , Adenina/análogos & derivados , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Aspergilose/tratamento farmacológico , Criptococose/tratamento farmacológico , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Imageamento por Ressonância Magnética/métodos , Meningoencefalite/tratamento farmacológico , Piperidinas , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Macroglobulinemia de Waldenstrom/complicações , Macroglobulinemia de Waldenstrom/tratamento farmacológicoRESUMO
PURPOSE: The prognosis of relapsing primary CNS lymphoma (PCNSL) is poor. We report the results of a prospective multicenter trial of intensive chemotherapy followed by autologous hematopoietic stem-cell rescue (IC + HCR) in immunocompetent adult patients with PCNSL or intraocular lymphoma (IOL) after failure of high-dose methotrexate-based treatment. PATIENTS AND METHODS: Salvage treatment consisted of two cycles of high-dose cytarabine and etoposide (CYVE). Intensive chemotherapy combined thiotepa, busulfan, and cyclophosphamide. Forty-three patients (median age, 52 years; range, 23 to 65 years) were included, with relapse (n = 22), refractory disease (n = 17), or a partial response to first-line treatment (n = 4). The response to CYVE was not assessable in three cases because of treatment-related death. Twenty patients (47%) were chemosensitive to CYVE: 15 of them proceeded to IC + HCR. IC + HCR was also administered to 12 patients who did not respond to CYVE. All but one of the 27 patients who underwent IC + HCR entered complete remission. RESULTS: With a median follow-up of 36 months, the median overall survival was 18.3 months in the overall population, and 58.6 months among patients who completed IC + HCR. The respective median progression-free survival (PFS) times after IC + HCR were 11.6 and 41.1 months. The 2-year overall survival probability was 45% in the whole population and 69% among the 27 patients who received IC + HCR. The 2-year PFS probability was 43% among all the patients and 58% in the IC + HCR subpopulation. CONCLUSION: IC + HCR is an effective treatment for refractory and recurrent PCNSL.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/terapia , Neoplasias Oculares/terapia , Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B/terapia , Recidiva Local de Neoplasia/terapia , Terapia de Salvação , Adulto , Idoso , Neoplasias Encefálicas/tratamento farmacológico , Bussulfano/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Etoposídeo/administração & dosagem , Neoplasias Oculares/tratamento farmacológico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Prospectivos , Taxa de Sobrevida , Tiotepa/administração & dosagemRESUMO
Angiogenesis plays an important role in the progression of tumors. This relationship has been described in several hematologic malignancies. Vascular endothelial growth factor and basic fibroblast growth factor are predictors of poor prognosis in leukemia and non Hodgkin's lymphoma. Bone marrow microvessels were found increased in multiple myeloma, but also in lymphoma and in acute lymphoblastic leukemia. Microvessel density is correlated with decreased survival in myeloma patients and relapse or resistance to chemotherapy in lymphoma. New drugs with antiangiogenic activity such as bevacizumab (binding and inactivation of VEGF) or VEGF-tyrosine kinase inhibitors have shown promising results in phase 1 trials. It will therefore be a future challenge to integrate anti-angiogenesis agents in currently existing treatment protocols to improve the outcome of therapy.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Neoplasias Hematológicas/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Inibidores da Angiogênese/fisiologia , Proteínas Angiogênicas/fisiologia , Fator 2 de Crescimento de Fibroblastos/fisiologia , Humanos , Leucemia/tratamento farmacológico , Linfoma/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Neovascularização Patológica/etiologia , Fator A de Crescimento do Endotélio Vascular/fisiologiaRESUMO
We described the ex vivo production of mature and functional human smooth muscle cells (SMCs) derived from skeletal myoblasts. Initially, myoblasts expressed all myogenic cell-related markers such as Myf5, MyoD and Myogenin and differentiate into myotubes. After culture in a medium containing vascular endothelial growth factor (VEGF), these cells were shown to have adopted a differentiated SMC identity as demonstrated by alphaSMA, SM22alpha, calponin and smooth muscle-myosin heavy chain expression. Moreover, the cells cultured in the presence of VEGF did not express MyoD anymore and were unable to fuse in multinucleated myotubes. We demonstrated that myoblasts-derived SMCs (MDSMCs) interacted with endothelial cells to form, in vitro, a capillary-like network in three-dimensional collagen culture and, in vivo, a functional vascular structure in a Matrigel implant in nonobese diabetic-severe combined immunodeficient mice. Based on the easily available tissue source and their differentiation into functional SMCs, these data argue that skeletal myoblasts might represent an important tool for SMCs-based cell therapy.
Assuntos
Diferenciação Celular , Colágeno/farmacologia , Laminina/farmacologia , Mioblastos Esqueléticos/fisiologia , Miócitos de Músculo Liso/fisiologia , Proteoglicanas/farmacologia , Técnicas de Cultura de Tecidos , Animais , Biomarcadores/análise , Células Cultivadas , Combinação de Medicamentos , Células Epiteliais/fisiologia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Fibras Musculares Esqueléticas/fisiologia , Mioblastos Esqueléticos/efeitos dos fármacos , Mioblastos Esqueléticos/metabolismo , Mioblastos Esqueléticos/transplante , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/transplante , Neovascularização Fisiológica , Transplante Heterólogo , Fator A de Crescimento do Endotélio Vascular/farmacologiaRESUMO
The case of an 80-year-old woman displaying myelodysplastic syndrome evolving into a myeloproliferative disorder with myelofibrosis and pulmonary fibrosis, is reported. This case is characterized by an initial presentation of a myelodysplastic syndrome with normal karyotype and moderate fibrosis, its evolution towards a myeloproliferative disorder with myelofibrosis and the worsening of pulmonary fibrosis in parallel to the acceleration of the myeloproliferative disorder and myelofibrosis. These features and the high concentration of plasma platelet factor-4 suggest a role of megakaryocyte/platelet degranulation in the development of fibrosis.