RESUMO
In the clinical settings, disseminated intravascular coagulation (DIC) and complications such as hemorrhage are commonly seen in acute promyelocytic leukemia patients, whereas thrombosis is rarely reported. We reported a case here that the patient presented with cerebral infarction as the first manifestation. During the admission, the patient encountered differentiation syndrome, pulmonary embolism, pulmonary hemorrhage, and myocardial ischemia, as well as bleeding and thrombosis complications. Hence the patient was diagnosed as DIC. After the treatment of blood transfusion instead of anticoagulation, his condition was stable and the remission was completely achieved. The treatment experience provides guides for other patients with similar complications of simultaneous bleeding and thrombosis.
Assuntos
Coagulação Intravascular Disseminada/etiologia , Leucemia Promielocítica Aguda/complicações , Trombose , Coagulação Sanguínea , Infarto Cerebral , HumanosRESUMO
MEK/ERK signal pathway was required for the differentiation of granulocytes, megakaryocytes and erythrocytes. Recently, MEK/ERK cascade was reported to be involved in all-trans retinoic acid (ATRA) induced differentiation in acute promyelocytic leukemia (APL) cells. However, the upstream and downstream molecules of MEK/ERK signal pathway in this cell model remains to be elucidated. In this work, we showed that RAF-1 was activated and the blockade of RAF-1 activation attenuated MEK/ERK activation as well as ATRA-induced differentiation. ATRA-enhanced protein levels of C/EBPß, C/EBPε and PU.1, which were required for differentiation in APL cells, were suppressed by the specific inhibitor of MEK. However, MEK inhibition had no effect on the degradation of PML-RARα fusion protein or the restoration of PML nuclear bodies by ATRA treatment. Taken together, our study suggested that RAF-1/MEK/ERK cascade was involved in ATRA-induced differentiation in APL cells through enhancing the protein level of C/EBPß, C/EBPε and PU.1.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Leucemia Promielocítica Aguda/patologia , Sistema de Sinalização das MAP Quinases/fisiologia , Proteínas Proto-Oncogênicas c-raf/fisiologia , Tretinoína/farmacologia , Antineoplásicos/farmacologia , Proteína beta Intensificadora de Ligação a CCAAT/biossíntese , Proteína beta Intensificadora de Ligação a CCAAT/efeitos dos fármacos , Proteínas Estimuladoras de Ligação a CCAAT/biossíntese , Proteínas Estimuladoras de Ligação a CCAAT/efeitos dos fármacos , Linhagem Celular Tumoral , Granulócitos/efeitos dos fármacos , Granulócitos/patologia , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/metabolismo , Proteínas Proto-Oncogênicas/biossíntese , Proteínas Proto-Oncogênicas/efeitos dos fármacos , Transativadores/biossíntese , Transativadores/efeitos dos fármacosRESUMO
All-trans retinoic acid (ATRA) resistance has been a critical problem in acute promyelocytic leukemia (APL) relapsed patients. In ATRA resistant APL cell lines NB4-R1 and NB4-R2, the combination of staurosporine and ATRA synergized to trigger differentiation accompanied by significantly enhanced protein level of CCAAT/enhancer binding protein ε (C/EBPε) and C/EBPß as well as the phosphorylation of mitogen-activated protein (MEK) and extracellular signal-regulated kinase (ERK). Furthermore, attenuation of the MEK activation blocked not only the differentiation but also the increased protein level of C/EBPε and C/EBPß. Taken together, we concluded that the combination of ATRA and staurosporine could overcome differentiation block via MEK/ERK signaling pathway in ATRA-resistant APL cell lines.