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1.
Cancers (Basel) ; 15(22)2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-38001691

RESUMO

Adult acute lymphoblastic leukemia (ALL) is associated with poor outcomes. ALL is initiated by primary aberrations, but secondary genetic lesions are necessary for overt ALL. In this study, we reassessed the value of primary and secondary aberrations in intensively treated ALL patients in relation to mutator enzyme expression. RT-PCR, genomic PCR, and sequencing were applied to evaluate primary aberrations, while qPCR was used to measure the expression of RAG and AID mutator enzymes in 166 adult ALL patients. Secondary copy number alterations (CNA) were studied in 94 cases by MLPA assay. Primary aberrations alone stratified 30% of the patients (27% high-risk, 3% low-risk cases). The remaining 70% intermediate-risk patients included BCR::ABL1pos subgroup and ALL lacking identified genetic markers (NEG ALL). We identified three CNA profiles: high-risk bad-CNA (CNAhigh/IKZF1pos), low-risk good-CNA (all other CNAs), and intermediate-risk CNAneg. Furthermore, based on RAG/AID expression, we report possible mechanisms underlying the CNA profiles associated with poor outcome: AID stratified outcome in CNAneg, which accompanied most likely a particular profile of single nucleotide variations, while RAG in CNApos increased the odds for CNAhigh/IKZF1pos development. Finally, we integrated primary genetic aberrations with CNA to propose a revised risk stratification code, which allowed us to stratify 75% of BCR::ABL1pos and NEG patients.

2.
Hematology ; 26(1): 556-564, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34384334

RESUMO

BACKGROUND: Azacitidine (AZA) is the standard of care for higher-risk myelodysplastic syndrome (HR-MDS) patients ineligible for intensive therapy. Clinical outcome discrepancies reported in clinical trials and real-life settings stimulate the search for new prognostic factors. METHODS: We retrospectively evaluated 315 MDS, 20-30% blast acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML) patients treated with azacitidine in 12 centers cooperating within the Polish Adult Leukemia Group (PALG). RESULTS: The median number of AZA cycles was 7 (1-69) and 24% patients received fewer than 4 cycles (early failure, EF). Serum albumin level was an independent predictor of EF occurrence. Complete remission (CR) was obtained in 20% and partial remission (PR) in 12% of patients. Hematologic improvement - erythroid (HI-E), neutrophil (HI-N), or platelet (HI-P) was achieved in 51%, 36%, and 48% of patients, respectively. No factors significantly predicted CR or PR in the multivariate analysis. For HI-E and HI-P, lower LDH level predicted response. Median survival was 15 (13-19) months. Lower serum albumin level, serious infection and receiving <4 AZA cycles independently predicted a worse overall survival (OS) (p < 0.05). CONCLUSION: Serum albumin assessment before azacitidine treatment can help to identify patients with higher risk of early failure and worse clinical outcome.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Síndromes Mielodisplásicas/tratamento farmacológico , Albumina Sérica Humana/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/sangue , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
3.
J Int Med Res ; 48(6): 300060520925693, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32527171

RESUMO

Acute graft-versus-host disease (aGvHD) reduces the efficiency and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In recent years, attempts have been made to transplant fecal microbiota from healthy donors to treat intestinal GvHD. This study presented two cases of patients undergoing allo-HSCT who were later selected for fecal microbiota transplantation (FMT). In the first patient, FMT resulted in the complete resolution of symptoms, whereas therapeutic efficacy was not achieved in the second patient. FMT eliminated drug-resistant pathogens, namely very drug-resistant Enterococcus spp., but not multidrug-resistant Acinetobacter baumannii or Candida spp. Further research is needed, particularly on the safety of FMT in patients with intestinal steroid-resistant GvHD and on the distant impact of transplanted microflora on the outcomes of allo-HSCT. FMT appears promising for the treatment of patients with steroid-resistant GvHD.


Assuntos
Disbiose/terapia , Transplante de Microbiota Fecal , Glucocorticoides/farmacologia , Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adulto , Biópsia , Resistência a Medicamentos , Disbiose/imunologia , Disbiose/microbiologia , Disbiose/patologia , Evolução Fatal , Microbioma Gastrointestinal/imunologia , Glucocorticoides/uso terapêutico , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/microbiologia , Doença Enxerto-Hospedeiro/patologia , Humanos , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/terapia , Masculino , Mielofibrose Primária/imunologia , Mielofibrose Primária/terapia , Transplante Homólogo/efeitos adversos , Resultado do Tratamento
4.
Adv Clin Exp Med ; 28(3): 385-390, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30525315

RESUMO

BACKGROUND: The PIM2 gene belongs to the PIM family, which encodes serine/threonine kinases involved in cell survival and apoptosis. The relation between the expression of the PIM2 gene and the course of chronic lymphocytic leukemia (CLL) has not been fully determined. OBJECTIVES: The aim of the study was to evaluate the role of the PIM2 gene as a marker of CLL malignancy and its importance as a predictive and prognostic factor. MATERIAL AND METHODS: Sixty-seven patients, 35 females and 32 males, aged 49-90 years, with de novo CLL, and 14 healthy individuals were enrolled in the study. Expression of the PIM2 gene was analyzed using TaqMan RQ-PCR assay and western blot test. RESULTS: Median PIM2 gene expression in CLL patients was higher than in controls. Patients with high expression of the PIM2 gene had shorter progression-free survival and time to first treatment than patients with low PIM2 expression. It was found that patients with CR had lower expression of the PIM2 gene than patients without complete remission (CR). Notably, associations between high PIM2 expression and rapid lymphocyte doubling time, the percentage of malignant lymphocytes with ZAP70 expression and the Rai stage were revealed. CONCLUSIONS: We found that the PIM2 gene is associated with a more aggressive clinical course of CLL.


Assuntos
Apoptose/genética , Leucemia Linfocítica Crônica de Células B/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Idoso , Idoso de 80 Anos ou mais , Feminino , Expressão Gênica , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/mortalidade , Linfócitos , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Taxa de Sobrevida , Proteína-Tirosina Quinase ZAP-70
5.
Hematol Oncol ; 2018 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-29512182

RESUMO

Atypical chronic myeloid leukaemia (aCML) belongs to myelodysplastic/myeloproliferative neoplasms. Because of its rarity and changing diagnostic criteria throughout subsequent classifications, data on aCML are very scarce. Therefore, we at the Polish Adult Leukemia Group performed a nationwide survey on aCML. Eleven biggest Polish centres participated in the study. Altogether, 45 patients were reported, among whom only 18 patients (40%) fulfilled diagnostic criteria. Among misdiagnosed patients, myelodysplastic/myeloproliferative syndrome unclassifiable and chronic myelomonocytic leukaemia were the most frequent diagnoses. Thirteen patients were male, median age 64.6 years (range 40.4-80.9). The median parameters at diagnosis were as follows: white blood cell count 97 × 109 /L (23.8-342) with immature progenitors amounting at 27.5% (12-72), haemoglobin 8.6 g/dL (3.9-14.9), and platelet count 66 × 109 /L (34-833). Cytoreductive treatment was used in all patients, and 2 patients underwent allogeneic hematopoietic stem cell transplantation. The median overall survival was 14.1 months (95% CI, 7.2), with median acute myeloid leukaemia-free survival of 13.3 months (95% CI, 3.6-22.6). Cumulative incidence of acute myeloid leukaemia transformation after 1 year in aCML group was 12.5% (95% CI, 0%-29.6%). To conclude, aCML harbours a poor prognosis. Treatment options are limited, with allogeneic hematopoietic stem cell transplantation being the only curative method at present, although only a minority of patients are transplant eligible. Educational measures are needed to improve the quality of diagnoses.

6.
Adv Clin Exp Med ; 27(1): 99-103, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29521049

RESUMO

BACKGROUND: Graves' orbitopathy (GO), also known as thyroid-associated ophthalmopathy, is characterized by dramatic tissue reactivity. Both inflammation and tissue remodeling characterize the clinical course of GO. Some data has been found regarding the association of MMPs and TIMPs in GO. MATERIAL AND METHODS: Serum concentrations of MMP-9, MMP-2, TIMP-1, and TIMP-2 were determined by ELISA method. OBJECTIVES: Forty-eight patients (34 females, 14 males, with median age 51.5 years) with GD and hyperthyroidism were enrolled in the study. In 28 patients, active, moderate-to-severe grade orbitopathy was diagnosed. The aim of this study was to assess the serum concentrations of MMP-2, MMP-9, TIMP-1, and TIMP-2 in patients with Graves' disease (GD), with and without GO, and their relationship with disease severity, as well as to evaluate how these concentrations change after successful treatment. RESULTS: Median serum concentrations of MMP-2 and MMP-9 were significantly higher in all patients with GD as well as in the subgroup with GO than in the control group. Median serum concentrations of TIMP-1 and TIMP-2 were significantly higher in all patients with GD than in controls. The same significant differences were observed in the subgroups with and without GO in comparison with controls. The GO subgroup showed a significant positive correlation between the MMP-9 concentration and the serum level of TSHRAb antibodies, and a clinical activity score ≥4 according to EUGOGO. CONCLUSIONS: In our study we found that only MMP-9 differentiates the patients with and without GO, and may be used as a marker of the disease severity in patients with this manifestation of GD.


Assuntos
Doença de Graves/sangue , Oftalmopatia de Graves/sangue , Metaloproteinase 2 da Matriz/sangue , Metaloproteinase 9 da Matriz/sangue , Inibidor Tecidual de Metaloproteinase-1/sangue , Inibidor Tecidual de Metaloproteinase-2/sangue , Idoso , Ensaio de Imunoadsorção Enzimática , Feminino , Doença de Graves/diagnóstico , Oftalmopatia de Graves/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade
8.
Dis Markers ; 2016: 7531472, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27818567

RESUMO

The Sokal, Hasford, and EUTOS scores were established in different treatment eras of chronic myeloid leukemia (CML). None of them was reported to predict molecular response. In this single center study we tried to reevaluate the usefulness of three main scores in TKI era. The study group included 88 CML patients in first chronic phase treated initially with standard imatinib dose. All of them achieved major molecular response (MMR) in time points defined by European LeukemiaNet (ELN). 42 patients lost MMR in a median time of 47 months and we found a significant difference in MMR maintenance between intermediate-risk (IR) and low-risk (LR) patients assessed by Hasford score. All 42 patients were switched to second-generation TKI (2G-TKI) treatment. At 18 months of 2G-TKI therapy we have still found a significant difference in BCR-ABL transcript levels and MMR rate between IR and LR groups. We did not find any of the described differences discriminating patients by Sokal or EUTOS score. In this retrospective single center analysis we found Hasford score to be useful in predicting molecular response in first chronic phase of CML patients.


Assuntos
Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Índice de Gravidade de Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais , Feminino , Seguimentos , Proteínas de Fusão bcr-abl/genética , Humanos , Técnicas Imunoenzimáticas , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Adulto Jovem
9.
Indian J Hematol Blood Transfus ; 32(Suppl 1): 143-7, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27408377

RESUMO

PURPOSE: Primary intraocular lymphoma (PIOL) is a rare malignancy with an aggressive clinical course. It is usually considered as a subset of primary central nervous system lymphoma. Differential diagnosis should include infectious and non-infectious aetiologies, particularly the common masqueraders sarcoidosis, tuberculosis, viral retinitis and syphilis. PATIENT: The article presents a case of bilateral vitreoretinal lymphoma manifesting as uveitis and vitritis resistant to corticosteroid therapy. The final diagnosis was based on a retinal biopsy. RESULTS: The patient was successfully treated with systemic and local therapy. Long-term complete remission (CR) was reached. The relapse of diffuse large B-cell lymphoma was revealed in the frontal left lobe after 48 months of CR duration. CONCLUSION: The diagnosis of PIOL is always very difficult. Cooperation of pathologists, ophthalmologists and hematologists is required for a quick and accurate diagnosis. Local and systemic treatment is needed to achieve CR, but the relapse rate remains very high.

10.
Leuk Lymphoma ; 57(9): 2140-9, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26764044

RESUMO

The PIM2 gene encodes the serine/threonine kinase involved in cell survival and apoptosis. The aim of the study was to evaluate the expression of the PIM2 gene in acute myeloid leukemia (AML) and to examine its role in apoptosis of the blastic cells. We analyzed the PIM2 expression in 148 patients: 91 with AML, 57 with acute lymphoblastic leukemia and 24 healthy controls by Real-Time PCR and Western blot. Inhibition of the PIM2 gene in human leukemic HL60 cell line was performed with RNAi and apoptosis rate was analyzed. Our results indicate that overexpression of PIM2 in AML is associated with low complete remission rate, high-risk cytogenetics, shorter leukemia-free survival, and event-free survival. Cytometric analysis of HL60/PAC-GFP and HL60/PAC-GFP-shPIM2 cells revealed an increase in the number of apoptotic cells after inhibition of PIM2 gene. In summary, the elevated expression of PIM2 in blastic cells is associated with poor prognosis of AML patients and their resistance to induction therapy.


Assuntos
Expressão Gênica , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose/genética , Biomarcadores Tumorais , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Fosforilação , Prognóstico , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Indução de Remissão , Adulto Jovem , Proteína de Morte Celular Associada a bcl/genética , Proteína de Morte Celular Associada a bcl/metabolismo
11.
Hematology ; 21(1): 26-33, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26268417

RESUMO

INTRODUCTION: Activity of metalloproteinases (MMP) is controlled both by specific tissue inhibitors (TIMP) and activators (extracellular matrix metalloproteinase inducer, EMMPRIN). There are few data available concerning concentration the bone marrow of MMP-2, MMP-9, TIMP-1, and TIMP-2, or EMMPRIM expression by bone marrow mesenchymal stromal cells (BMSCs) in patients with multiple myeloma (MM). PATIENTS AND METHODS: We studied 40 newly diagnosed, untreated patients: 18 males and 22 females with de novo MM and 11 healthy controls. Bone marrow was collected prior to therapy. BMSCs were derived by culturing bone marrow cells on MesenCult. Protein concentrations were determined in bone marrow plasma and culture supernatants by ELISA. EMMPRIN expression by BMSCs was assessed by flow cytometry. RESULTS: The median concentrations of MMP-9, TIMP-1, and TIMP-2 in both marrow plasma and culture supernatants were significantly higher in MM patients than controls. CONCLUSION: EMMPRIN expression and ratios MMP-9/TIMP-1 and MMP-2/TIMP-2 were higher in MM patients, our results demonstrate that in MM patients MMP-2 and MMP-9 are secreted in higher amounts and are not balanced by inhibitors.


Assuntos
Basigina/genética , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Mieloma Múltiplo/genética , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-2/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Basigina/metabolismo , Medula Óssea/metabolismo , Medula Óssea/patologia , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/patologia , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Cultura Primária de Células , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo
12.
Int J Hematol ; 102(3): 364-7, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26121955

RESUMO

Hemorrhagic cystitis (HC) is a diffuse inflammation of the bladder of an infectious or non-infectious etiology, causing bleeding of the bladder mucosa. There are no explicit guidelines defining the appropriate treatment of HC. Hyperbaric oxygen therapy (HBO) is a non-invasive method involving the use of 100 % oxygen under increased pressure, which penetrates to poorly perfused areas. The most appropriate group for treatment with HBO is patients with BK virus-associated HC after allogenic human stem cell transplantation (alloHSCT). In this report, we present five patients after alloHSCT from a matched unrelated donor with symptoms of HC successfully treated with HBO. All patients received therapy with 100 % oxygen in a hyperbaric chamber at 2.5 atmospheres for 60 min, delivered 5 days per week. Complete response with resolution of pain and hematuria, as well as eradication of viral load, was achieved by all the patients after a mean of 13 sessions (range 11-30) of HBO. These data indicate that HBO therapy is sufficient and effective in the treatment of HC, and represents a well-tolerated procedure with good clinical and laboratory results after ineffective primary treatment.


Assuntos
Cistite/terapia , Transplante de Células-Tronco Hematopoéticas , Hemorragia/terapia , Oxigenoterapia Hiperbárica , Doadores não Relacionados , Adulto , Aloenxertos , Cistite/etiologia , Feminino , Hemorragia/etiologia , Humanos , Masculino , Fatores de Tempo
13.
Adv Clin Exp Med ; 24(6): 1113-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26771986

RESUMO

Fungal infections of the eye are an important cause of significant visual loss and blindness in some regions of the world, especially developing countries. Ocular mycoses remain a diagnostic and therapeutic challenge to the ophthalmologist. Corneal infection is the most frequent presentation, but the orbit, eyelids, lacrimal apparatus, conjunctiva, sclera and internal structures of the eye can also be affected. Candida spp., Fusarium spp. and Aspergillus spp. are the most frequently isolated organisms in fungal keratitis and in endophthalmitis. The difficulties posed by ocular mycoses are mainly related to establishing the clinical diagnosis, isolation of the fungal pathogen and effective local treatment, particularly in infections of the cornea. The critical issue in diagnosing fungal infection of the eye is microbiological identification of the etiologic agent in clinical samples. Early diagnosis and prompt treatment allow serious complications, including blindness, to be avoided. Local, systemic and even surgical treatment is applied in the therapy.


Assuntos
Infecções Oculares Fúngicas , Antifúngicos/uso terapêutico , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/microbiologia , Humanos , Valor Preditivo dos Testes , Fatores de Risco , Resultado do Tratamento
14.
Acta Haematol ; 132(2): 166-71, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24577437

RESUMO

BACKGROUND: Chronic myeloid leukemia (CML) biology seemed to be perfectly explored especially at the beginning of the tyrosine kinase inhibitors era. Later years with imatinib and second-generation tyrosine kinase inhibitors showed a variety of resistance mechanisms and it became obvious that the bcr-abl chimeric gene is not the only enemy to fight. Some studies assumed the decreased rate of programmed cell death (apoptotic) to be the primary mechanism by which BCR-ABL affects expansion of the leukemic clone in CML. Therefore, the aim of this study was to investigate the role of c-kit inhibition in treatment response. METHODS: Cytogenetic analysis, real-time quantitative reverse-transcriptase polymerase chain reaction, flow-cytometric analysis and imatinib serum level quantification were applied. RESULTS: The percentage of CD34+ cells expressing c-kit (CD117) isolated from bone marrow samples of 54 CML patients treated with standard-dose imatinib was significantly lower among imatinib responders. The fraction of apoptotic CD34+CD117+ cells in this patient group was significantly higher than in nonresponders. CONCLUSION: To achieve optimal treatment response in CML patients, the elimination of CD34+CD117+ may be necessary through an apoptotic pathway.


Assuntos
Antineoplásicos/uso terapêutico , Benzamidas/uso terapêutico , Medula Óssea/patologia , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Proteínas de Neoplasias/antagonistas & inibidores , Células-Tronco Neoplásicas/efeitos dos fármacos , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-kit/antagonistas & inibidores , Pirimidinas/uso terapêutico , Adulto , Idoso , Antígenos CD34/análise , Antineoplásicos/sangue , Antineoplásicos/farmacologia , Apoptose , Benzamidas/sangue , Benzamidas/farmacologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Citometria de Fluxo , Humanos , Mesilato de Imatinib , Imunofenotipagem , Leucemia Mieloide de Fase Crônica/enzimologia , Leucemia Mieloide de Fase Crônica/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/fisiologia , Células-Tronco Neoplásicas/enzimologia , Células-Tronco Neoplásicas/patologia , Piperazinas/sangue , Piperazinas/farmacologia , Inibidores de Proteínas Quinases/sangue , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-kit/fisiologia , Pirimidinas/sangue , Pirimidinas/farmacologia , Reação em Cadeia da Polimerase em Tempo Real , Indução de Remissão
15.
Postepy Hig Med Dosw (Online) ; 67: 553-9, 2013 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-23752607

RESUMO

INTRODUCTION: PIM-2 is a proto-oncogene that encodes for a serine/threonine kinase that interacts with various signaling molecules. PIM-2 is highly expressed in neoplastic tissues and in leukemic and lymphoma cell lines, which is consistent with its role during oncogenic transformation. The nuclear factor kappa B (NF-κB) pathway appears to be deregulated in a variety of tumors, with sustained activity of NF-κB leading to apoptotic resistance in tumor cells. The aim of this study was to investigate whether expression of PIM-2 and NF-κB is altered in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: One hundred forty-three patients were included: 91 with AML and 52 with ALL, aged 18-84 (median 46.7). Eighty-three patients (51 AML and 32 ALL) reached complete remission (CR). Bone marrow samples were collected at the time of diagnosis. Control samples were obtained from 24 healthy donors. We analyzed PIM-2 and NF-κB expression by RQ-PCR analysis. RESULTS: Expression of both PIM-2 and NF-κB in all leukemia patients and subgroups was significantly higher than in controls. AML patients who reached CR expressed PIM-2 and NF-κB at significantly lower levels than did patients with primary resistance to chemotherapy and who did not reach CR (NCR). Survival analysis revealed that in AML patients with higher expression of PIM-2 the overall survival (OS) was significantly shorter than in patients with lower expression. CONCLUSION: Our data indicate that PIM-2 and NF-κB gene expression is increased in patients with AML and ALL. Moreover, high PIM-2 expression is associated with CR rate and OS in AML patients.


Assuntos
Medula Óssea/metabolismo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , NF-kappa B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/patologia , Linhagem Celular Tumoral , Feminino , Expressão Gênica , Humanos , Leucemia Mieloide Aguda/metabolismo , Masculino , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas/metabolismo , Valores de Referência , Indução de Remissão , Taxa de Sobrevida , Adulto Jovem
16.
Endocr Res ; 37(2): 89-95, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22489922

RESUMO

BACKGROUND: The extrathyroid, orbital manifestation of Graves' disease (GD)--Graves' orbitopathy (GO)--presents a difficult clinical problem. The immunological status of GO patients is still under investigation. The aim of this study was to assess the serum concentration of interleukin 6 (IL-6), soluble interleukin 6 receptor (sIL-6R), and CD8+CD28- lymphocytes in GO patients and to evaluate if these parameters were associated with disease activity. PATIENTS: Thirty-nine patients (29 women and 10 men, aged 24-71, mean 50.18) with newly diagnosed GD were enrolled in the study. Active GO was diagnosed in 20 patients. The control group included 12 healthy individuals. METHODS: Serum concentrations of IL-6 and sIL-6R were estimated by ELISA. Percentages of CD8+CD28- lymphocytes in peripheral blood were assessed by flow cytometry. RESULTS: Mean serum IL-6 and sIL-6R concentrations were significantly higher in all GD patients and in GO and non-GO patients than in normal controls. In all GD patients and the non-GO group, serum IL-6 and sIL-6R concentrations were significantly reduced after efficient treatment. In GO patients, only serum sIL-6R concentration was significantly lower after efficient treatment. In all GD patients, the mean percentage of CD8+CD28- lymphocytes was significantly lower after efficient treatment. In GO patients, the mean percentage of CD8+CD28- lymphocytes was significantly higher than in the non-GO group or in normals. Moreover, in the GO group, the mean percentage of CD8+CD28- lymphocytes was significantly lower after treatment. CONCLUSION: Our results have shown that CD8+CD28- lymphocyte percentage in peripheral blood and serum concentration of sIL-6R are increased in GO patients and correlate with disease activity.


Assuntos
Antígenos CD28/sangue , Linfócitos T CD8-Positivos/imunologia , Oftalmopatia de Graves/sangue , Oftalmopatia de Graves/imunologia , Receptores de Interleucina-6/sangue , Adulto , Idoso , Feminino , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade
17.
Postepy Hig Med Dosw (Online) ; 63: 355-9, 2009 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-19644152

RESUMO

INTRODUCTION: T cells with the CD8+CD28- phenotype are CD8+ lymphocytes with regulatory function. Their increased numbers were observed in infections, autoimmune and neoplastic diseases, and in elderly healthy individuals. CD8+CD28- lymphocyte levels in patients with cutaneous T-cell lymphoma (CTCL) has not yet been described. The aim of the study was to determine their levels in these patients' peripheral blood and cutaneous infiltrates and their relation to the clinical stage of disease. MATERIAL/METHODS: Forty-one untreated patients, 26 males and 15 females, with CTCL were enrolled in the study. CD8+CD28- lymphocyte levels were determined by flow cytometry in peripheral blood and by immunochemistry in skin infiltrates. RESULTS: The percentage of CD8+CD28- lymphocytes in the peripheral blood of the patients was significantly higher than in the controls. Patients with advanced disease displayed a higher percentage of CD8+CD28- lymphocytes in the peripheral blood and skin than did the individuals with early stages of the disease. Moreover, positive correlations between CD8+CD28- lymphocyte level in peripheral blood and age, clinical stage, and the levels in the skin infiltrates was revealed. Additionally, the percentage of CD8+CD28- T cells in the skin infiltrates correlated positively with age and clinical stage of the disease. CONCLUSIONS: These data suggest that CD8+CD28- lymphocytes play an important role in the development of immunotolerance in the progression of cutaneous T-cell lymphoma.


Assuntos
Antígenos CD28/sangue , Linfoma Cutâneo de Células T/sangue , Neoplasias Cutâneas/sangue , Subpopulações de Linfócitos T/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD28/imunologia , Estudos de Casos e Controles , Feminino , Humanos , Linfoma Cutâneo de Células T/imunologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Cutâneas/imunologia
18.
Eur J Haematol ; 82(4): 260-6, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19187271

RESUMO

Previous studies showed that peripheral blood lymphocytes of B-cell chronic lymphocytic leukemia (B-CLL) displayed a high intracellular level of cell cycle inhibitory protein p27(Kip1). It has been suggested that its' high expression may confer them survival advantage and lead to unfavorable prognosis, but the prognostic significance of p27(Kip1) expression for previously untreated, non-advanced stage B-CLL was not established. We studied a relationship between the intracellular level of p27(Kip1) of lymphocytes of early- and intermediate stage B-CLL patients and their spontaneous apoptosis in vitro, as well as prognostic significance of p27(Kip1) in B-CLL lymphocytes for the risk of disease progression. Intracellular p27(Kip1) content of peripheral blood lymphocytes obtained from 48 previously untreated 0-II Rai stage B-CLL patients was determined by flow cytometry. The viability and apoptosis of those lymphocytes after 72-h culture were also assessed. During the follow-up period (6-71 months, median 59.5), we recorded the time elapsed to the doubling of lymphocyte count, progression to a higher Rai stage and the appearance of indications for cytostatic treatment. The p27(Kip1) expression was neither correlated with initial lymphocyte count, CD38 expression, cell viability nor spontaneous apoptosis ratio after 72-h culture. Higher p27(Kip1) level was related to the probability of earlier occurrence of each of three above-mentioned events. We did not find a prognostic significance of in vitro cell viability nor apoptosis as to the risk of disease progression. Our results indicate that elevated intracellular p27(Kip1) level in leukemic lymphocytes of early- and intermediate stage B-CLL patients contributes to rapid progression of the disease.


Assuntos
Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Leucemia Linfocítica Crônica de Células B/metabolismo , Linfócitos/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/análise , Apoptose , Linfócitos B/citologia , Linfócitos B/fisiologia , Divisão Celular , Inibidor de Quinase Dependente de Ciclina p27/genética , Progressão da Doença , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Leucemia Linfocítica Crônica de Células B/mortalidade , Leucemia Linfocítica Crônica de Células B/patologia , Linfócitos/citologia , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Valores de Referência , Análise de Sobrevida , Sobreviventes
19.
Mediators Inflamm ; 2006(3): 42394, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16951490

RESUMO

Syndecan-1 (CD138) is a transmembrane heparin sulfate proteoglycan expressed on distinct stages of differentiation of B-lymphoid cells. Its prognostic value in B-cell chronic lymphocytic leukemia (B-CLL) has not been evaluated so far. The serum concentration of sCD138 and some angiogenesis-involved cytokines: vascular endothelial growth factor (VEGF), basis fibroblast growth factor (bFGF), and endostatin were studied in 52 previously untreated patients with B-CLL. We found that bFGF and sCD138 levels were significantly higher in B-CLL patients than in controls. In patients with sCD138 level or endostatin level below the median value the lymphocyte count was higher than in patients with serum level of those cytokines above the median value. In patients with progressive disease bFGF level was significantly higher and sCD138 level significantly lower than in patients with stable one. Moreover, high sCD138 level was associated with longer lymphocyte doubling-free survival, and, on the limit of statistical significance, a high endostatin level was associated with shorter progression-free survival. We conclude that serum sCD138 level is increased in early stage B-CLL patients and may have a positive prognostic value as to the dynamics of the disease.


Assuntos
Endostatinas/sangue , Fator 2 de Crescimento de Fibroblastos/sangue , Leucemia Linfocítica Crônica de Células B/sangue , Glicoproteínas de Membrana/sangue , Proteoglicanas/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Sindecana-1 , Sindecanas
20.
Med Sci Monit ; 8(5): BR175-8, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-12011765

RESUMO

BACKGROUND: Monitoring of disease activity and effectiveness of treatment plays an important role in curative management of patients with non-Hodgkin's lymphomas (n-HL). In the search for markers useful for biochemical monitoring of n-HL patients, a group of proteins called adhesion molecules attracted attention. Particular attention has been devoted to sICAM-1 (intercellular adhesion molecule-1). A correlation between sICAM-1 levels and histological malignancy grades and clinical staging of n-HL, activity of the disease and tumor mass has been observed. The aim of the study was to assess the utility of determining serum levels of selected adhesion molecules in n-HL monitoring. The study was carried out in 60 patients with intermediate and high malignancy grade n-HL according to Working Formulation (anaplastic, lymphoblastic, immunoblastic, centroblastic and centroblastic-centrocytic). MATERIAL/METHODS: Soluble ICAM-1 adhesion molecule (sICAM-1) and selectin E levels were determined in the sera of 31 newly diagnosed patients, 18 with complete remission, and 11 with relapse of the disease. The control group consisted of 15 healthy subjects. The results were expressed in ng/ml. RESULTS: sICAM1 levels were similar in healthy controls and patients in the remission phase and significantly lower in patients with diagnosed active disease and relapses. Relapses were associated with slightly lower levels (on borderline of statistical significance) than of diagnosis Serum selectin E levels, however, demonstrated no differences among patient groups or as compared with controls. CONCLUSIONS: The presented results indicate the utility of serum sICAM-1 level determination in assessment of activity of intermediate and high malignancy grade non-Hodgkin's lymphomas.


Assuntos
Selectina E/sangue , Molécula 1 de Adesão Intercelular/sangue , Linfoma não Hodgkin/sangue , Adolescente , Adulto , Estudos de Casos e Controles , Adesão Celular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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