RESUMO
Most hematological malignancies are characterized by overexpression of certain cancer promoting genes, such as MYC, MCL1 and cyclin D1. Preclinical studies in animal models have shown that CDK9 inhibitors supress the transcription of these anti-apoptotic and pro-survival proteins, and suggest their potential synergism with other drugs. In its first in-human trial, enitociclib demonstrated clinical activity in a small cohort of patients with high grade B lymphoma with MYC and BCL2 and/or BCL6 rearrangements, inducing complete responses in 2 of 7 subjects (29%) in monotherapy. These data suggest CDK9 inhibitors could play a role in the treatment of hematological diseases and could be a great ally when combined with other therapeutic approaches.
Assuntos
Quinase 9 Dependente de Ciclina , Neoplasias Hematológicas , Linfoma Difuso de Grandes Células B , Animais , Humanos , Quinase 9 Dependente de Ciclina/antagonistas & inibidores , Rearranjo Gênico , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/genética , Linfoma Difuso de Grandes Células B/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Indução de RemissãoRESUMO
No disponible
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Trombocitopenia/complicações , Disartria/diagnóstico , Acidente Vascular Cerebral/diagnóstico por imagem , Plasmaferese , Corticosteroides/uso terapêutico , Diagnóstico Precoce , Acidente Vascular Cerebral/complicações , Pronação , Doenças Hematológicas/complicações , Doenças Hematológicas/etiologia , Diagnóstico DiferencialRESUMO
Most α-thalassemia cases are caused by deletions of the structural α-globin genes. The degree of microcytosis and hypochromia has been correlated with the number of affected α-globin genes, suggesting a promising role of hematologic parameters as predictive diagnostic tools. However, cut-off points for these parameters to discriminate between the different subtypes of α-thalassemia are yet to be clearly defined. Six hematologic parameters (RBC, Hb, MCV, MCH, MCHC and RDW) were evaluated in 129 cases of deletional α-thalassemia (56 heterozygous α⺠thalassemia, 36 homozygous α⺠thalassemia, 29 heterozygous α° thalassemia and 8 cases of Hb H disease). A good correlation between the number of deleted alpha genes and MCV (r = -0.672, p < 0.001), MCH (r = -0.788, p < 0.001) and RDW (r = 0.633, p < 0.001) was observed. The presence of an α° allele should be discarded in individuals with microcytosis without iron deficiency and normal values of Hb A2 and Hb F with MCH < 23.40 pg. Furthermore, MCH < 21.90 pg and/or MCV < 70.80 fL are strongly suggestive of the presence of one α° allele. Finally, an accurate presumptive diagnosis of Hb H disease can be made if both RDW ≥ 20% and MCH < 19 pg are seen.
