Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute promyelocytic leukemia is a clonal expansion of malignant cells blocked at a specific stage of myeloid differentiation. The disease is associated with a specific translocation between chromosome 17 and chromosome 15 [t(15;17)] and with a bleeding diathesis previously attributed to disseminated intravascular coagulation, which has recently also been related to primary fibrinolysis. The high percentage of early deaths, about 20%, experienced by acute promyelocytic leukemia patients, is generally due to the hemorrhagic syndrome. A new finding is the high effectiveness of treatment with all-trans retinoic acid, a vitamin A derivative, for inducing complete remission. The induction of cellular maturation by this agent represents the first model of differentiation therapy. Furthermore, recent molecular studies revealed that the breakpoints of the t(15;17) translocation are clustered in the gene of retinoic acid receptor-alpha, generating a hybrid gene product. Gene transfection experiments disclosed the impairment of gene transactivation due to the hybrid gene products, opening new concepts for understanding leukemogenesis. Understanding the mechanisms of action of retinoic acid could extend differentiation therapy to other malignancies with aberrant gene transcription.
 ...
PMID:Retinoic acid in acute promyelocytic leukemia: a model for differentiation therapy. 131 15

Acute promyelocytic leukemia (APL) is a clonal expansion of malignant cells blocked at a specific stage of myeloid differentiation. The disease is associated with a specific translocation between chromosome 17 and chromosome 15 t (15; 17) and with a bleeding diathesis previously attributed to a disseminated intravascular coagulation which is recently also related to a primary fibrinolysis. The high percentage of early deaths, around 20% experienced by APL patients, is generally due to the haemorrhagic syndrome. A new feature is the highly effectiveness of all-trans retinoic acid treatment, a vitamin A derivative, for inducing complete remission in patients. The induction of cellular maturation by this agent represents the first model of differentiation therapy. Furthermore recent molecular studies revealed that the breakpoints of the t(15; 17) translocation are clustered in the gene of retinoic acid receptor a, generating a hybrid gene product. Gene transfection experiments disclosed the impairment of gene transactivation due to the hybrid gene products, opening new concepts for the leukemogenesis. The abnormal program made by the aberrant transcript might be overcome by pharmacological concentration of RA which induces an over expression of the normal allele and a normal activity of the aberrant product.
 ...
PMID:Phenotypic reversion in acute promyelocytic leukemia. 166 50