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

Myelodysplastic syndrome (MDS) is a hematopoietic stem-cell disorder characterized by trilineage dysplasia and susceptibility to acute myelogenous leukemia (AML). Analysis of molecular basis of MDS has been hampered by the heterogeneity of the disease. Recently, mutations of the transcription factor AML1/RUNX1 have been identified in 15% to 40% of MDS-refractory anemia with excess of blasts (RAEB) and MDS/AML. We performed mouse bone marrow transplantation (BMT) using bone marrow cells transduced with the AML1 mutants. Most mice developed MDS and MDS/AML-like symptoms within 4 to 13 months after BMT. Interestingly, among integration sites identified, Evi1 seemed to collaborate with an AML1 mutant harboring a point mutation in the Runt homology domain (D171N) to induce MDS/AML with an identical phenotype characterized by marked hepatosplenomegaly, myeloid dysplasia, leukocytosis, and biphenotypic surface markers. Collaboration between AML1-D171N and Evi1 was confirmed by a BMT model where coexpression of AML1-D171N and Evi1 induced acute leukemia of the same phenotype with much shorter latencies. On the other hand, a C-terminal truncated AML1 mutant (S291fsX300) induced pancytopenia with erythroid dysplasia in transplanted mice, followed by progression to MDS-RAEB or MDS/AML. Thus, we have developed a useful mouse model of MDS/AML that should help in the understanding of the molecular basis of MDS and the progression of MDS to overt leukemia.
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PMID:AML1 mutations induced MDS and MDS/AML in a mouse BMT model. 1843 65

Congenital leukemia is very rare, and its prevalence according to recently published papers is from 1 to 5 per million live births. This can be often diagnosed in postpartum throughout bone marrow biopsy, showing abnormal proliferation of immature blasts and granulocytic precursors. Hepatosplenomegaly is the most common feature which is found during perinatal examinations, that diagnosing is difficult during perinatal period. Hepatosplenomegaly can occur not only in congenital leukemia but in many other cases such as infection which is the most common cause. In other words, congenital leukemia is the one of the rare causes of hepatosplenomegaly. However, this case shows the fetus with the features of hepatosplenomegaly during perinatal period and being diagnosed as congenital leukemia associated with acquired AML1 gene duplication in postpartum through bone marrow biopsy. Due to its rare instance, we are to describe the case with a review of literatures.
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PMID:Congenital leukemia of fetus with acquired AML1 gene duplication. 2510 8