RESUMO
Sixty-four patients < 20 years of age, investigated for a suspicion of Philadelphia-negative myeloproliferative disease (MPD), were retrospectively evaluated to characterize the different forms and to examine the treatments used and long-term outcome. JAK2 mutations, endogenous erythroid colony growth, and clonality were investigated in 51 children. Mutations of thrombopoietin, the thrombopoietin receptor (MPL), and the erythropoietin receptor and mutations of other genes involved in the pathogenesis of MPD were investigated in JAK2 wild-type patients. Based on our criteria for childhood MPD, we identified 34 patients with sporadic thrombocythemia (ST), 16 with hereditary thrombocytosis (HT), 11 with sporadic polycythemia (SP), and 3 with hereditary polycythemia (HP). JAK2(V617F) mutations were present in 47.5% of ST and in no HT. The MPL(S505A) mutation was detected in 15/16 HT patients and in no ST (P < .00001). The JAK2(V617F) mutation occurred in 27% of SP patients diagnosed according to the Polycythemia Vera Study Group or World Health Organization 2001 criteria. Children with ST received more cytoreductive drugs than those with HT (P = .0006). After a median follow-up of 124 months, no patient had developed leukemia or myelofibrosis and 5% had thrombosis; the miscarriage rate in thrombocythemic patients was 14%. The low complication rate in our population suggests that children with MPD may be managed by tailored approaches.
Assuntos
Policitemia/tratamento farmacológico , Trombocitemia Essencial/tratamento farmacológico , Trombocitose/tratamento farmacológico , Adolescente , Substituição de Aminoácidos , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Janus Quinase 2/genética , Masculino , Mutação , Policitemia/complicações , Policitemia/genética , Gravidez , Complicações Hematológicas na Gravidez , Resultado da Gravidez , Receptores de Trombopoetina/genética , Estudos Retrospectivos , Trombocitemia Essencial/complicações , Trombocitemia Essencial/genética , Trombocitose/complicações , Trombocitose/genética , Resultado do Tratamento , Adulto JovemRESUMO
The methylenetetrahydrofolate reductase C677T mutation, factor V G1691A (factor V Leiden) mutation, prothrombin G20210A mutation and 8 other laboratory values associated with increased thrombotic risk were analyzed in 40 patients with sudden sensorineural hearing loss (SSHL). The results were compared with those obtained from 120 controls not affected by SSHL. We found a statistically significant higher frequency of hyperhomocysteinemia in the SSHL group compared with controls, and that this was also associated with the presence of homozygosity for the MTHFR C677T mutation. The study results suggest that SSHL might be caused, among other factors, by a combination of these 2 variables. We suggest that this analysis of the MTHFR C677T mutation should be further investigated to establish the etiology of SSHL, and that the same analysis should be taken into account in those patients with high levels of homocysteine.
Assuntos
Fator V/genética , Predisposição Genética para Doença , Perda Auditiva Neurossensorial/genética , Perda Auditiva Súbita/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Protrombina/genética , Adulto , Idoso , Alelos , Feminino , Genótipo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Mutação , Fatores de RiscoAssuntos
Púrpura Trombocitopênica Trombótica/complicações , Trombofilia/complicações , Trombofilia/genética , Adulto , Idoso , Fator V/genética , Feminino , Humanos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Pessoa de Meia-Idade , Mutação , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/genética , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Trombofilia/diagnósticoRESUMO
MUC1 is a large surface glycoprotein expressed by epithelial cells, which is overexpressed and aberrantly glycosylated in carcinomas. MUC1 is involved in epithelial cell interactions and appears to function as a signal-transducing molecule. The finding that MUC1 can also be expressed in the haematopoietic lineages prompted us to further investigate the possible function(s) of this molecule in haematopoietic cells. In bone marrow differentiating cells, MUC1 was strongly and selectively expressed during erythropoiesis; it was also weakly expressed during megakaryocytopoiesis and granulomonocytopoiesis; however, no correlation between MUC1 and differentiation marker expression was observed in these lineages. In vitro CD34+ cells, induced towards erythroid differentiation, acquired MUC1 transiently, while expressing increasing levels of the lineage marker glycophorin A. MUC1 was absent in the circulating erythrocytes. During erythropoiesis, MUC1 expression was transcriptionally regulated and the molecule underwent phosphorylation. To investigate the possible role of MUC1 during erythropoiesis, we studied the ability of MUC1 to act as ligand for cell-cell interaction. The sialylated MUC1 glycoforms selectively expressed on erythroid cells were able to bind the macrophage-restricted molecule sialoadhesin. These results suggest that MUC1 can function as a cross-talk molecule between the erythroblasts and the surrounding cells during erythropoiesis.