Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019214 (hepatosplenomegaly)
 4,408 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case of congenital hemolytic anemia caused by pyruvate kinase (PK) deficiency variant designated PK 'Nichinan' is presented. A 29-old patient with a history of anemia and hepatosplenomegaly had an episode of aplastic crisis associated with fever, abdominal symptoms and worsening hepatosplenomegaly. Study of the family members revealed that his mother and two of three siblings showed decreased PK activity whereas his father showed normal PK activity with a normal level of glycolytic intermediates. The patient was assumed to be a double heterozygote with two separate mutant genes from the parents despite the apparent normality of his father's erythrocyte PK.
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PMID:A family case of pyruvate kinase variant, PK 'Nichinan'. 223 65

Significant hyperbilirubinaemia, anemia, and splenomegaly are common features in patients with severe haemolysis due to pyruvate kinase (PK) deficiency. Until now, severe neonatal PK deficiency has not been associated with fatal liver disease at this age. We present two neonatal cases of severe PK deficiency complicated with progressive fatal liver disease. The patients presented with severe haemolysis, progressive cholestasis, and hepatosplenomegaly, and both patients ultimately developed liver failure at a very young age. Despite extensive investigations, no specific explanation for liver disease and failure was found. We suggest that the PK deficiency itself directly led to liver dysfunction.
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PMID:Pyruvate kinase deficiency associated with severe liver dysfunction in the newborn. 1765 6

Therapy based on targeted inhibition of BCR-ABL tyrosine kinase has greatly improved the prognosis for patients with Philadelphia chromosome (Ph)-positive leukemia and tyrosine kinase inhibitors (TKI) have become standard therapy. However, some patients acquire resistance to TKI that is frequently associated with point mutations in BCR-ABL. We previously reported that a medium-chain fatty-acid derivative AIC-47 induced transcriptional suppression of BCR-ABL and perturbation of the Warburg effect, leading to growth inhibition in Ph-positive leukemia cells. Herein, we showed that AIC-47 had anti-leukemic effects in either wild type (WT)- or mutated-BCR-ABL-harboring cells. AIC-47 suppressed transcription of BCR-ABL gene regardless of the mutation through downregulation of transcriptional activator, c-Myc. Reprogramming of the metabolic pathway has been reported to be associated with resistance to anti-cancer drugs; however, we found that a point mutation of BCR-ABL was independent of the profile of pyruvate kinase muscle (PKM) isoform expression. Even in T315I-mutated cells, AIC-47 induced switching of the expression profile of PKM isoforms from PKM2 to PKM1, suggesting that AIC-47 disrupted the Warburg effect. In a leukemic mouse model, AIC-47 greatly suppressed the increase in BCR-ABL mRNA level and improved hepatosplenomegaly regardless of the BCR-ABL mutation. Notably, the improvement of splenomegaly by AIC-47 was remarkable and might be equal to or greater than that of TKI. These findings suggest that AIC-47 might be a promising agent for overcoming the resistance of Ph-positive leukemia to therapy.
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PMID:Potent antiproliferative effect of fatty-acid derivative AIC-47 on leukemic mice harboring BCR-ABL mutation. 3054 79