Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Nucleophosmin1 (NPM1) gene located in chromosome 5q35 is affected by chromosomal translocation, mutation and deletion in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). NPM1 haploinsufficiency reportedly causes MDS-like disorders in knockout mice. Here, we studied mRNA and protein expression in bone marrow (BM) samples from 36 patients with MDS. The NPM1 expression levels of mRNA and protein were not related to chromosome 5 abnormalities and were almost the same as those in normal BM and AML cells. However, the protein levels in AML cells with NPM1 mutations were slightly lower than in those without mutation. Immunochemical studies showed no difference in the staining intensity and subcellular localisation between MDS and normal BM cells. It was concluded that abnormal cytoplasmic localisation and/or significant reduction of NPM1 protein level rarely occurs in MDS. The increase in the number of nuclear NPM1-positive cells may be related to the progression of MDS.
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PMID:Abnormal cytoplasmic dyslocalisation and/or reduction of nucleophosmin protein level rarely occurs in myelodysplastic syndromes. 1905 85

Nucleophosmin (NPM1) gene mutations rarely occur in non-acute myeloid neoplasms (MNs) with <20% blasts. Among nearly 10,000 patients investigated so far, molecular analyses documented NPM1 mutations in around 2% of myelodysplastic syndrome (MDS) cases, mainly belonging to MDS with excess of blasts, and 3% of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) cases, prevalently classified as chronic myelomonocytic leukemia. These uncommon malignancies are associated with an aggressive clinical course, relatively rapid progression to overt acute myeloid leukemia (AML) and poor survival outcomes, raising controversies on their classification as distinct clinico-pathologic entities. Furthermore, fit patients with NPM1-mutated MNs with <20% blasts could benefit most from upfront intensive chemotherapy for AML rather than from moderate intensity MDS-directed therapies, although no firm conclusion can currently be drawn on best therapeutic approaches, due to the limited available data, obtained from small and mainly retrospective series. Caution is also suggested in definitely diagnosing NPM1-mutated MNs with blast count <20%, since NPM1-mutated AML cases frequently present dysplastic features and multilineage bone marrow cells showing abnormal cytoplasmic NPM1 protein delocalization by immunohistochemical staining, therefore belonging to NPM1-mutated clone regardless of blast morphology. Further prospective studies are warranted to definitely assess whether NPM1 mutations may become sufficient to diagnose AML, irrespective of blast percentage.
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PMID:NPM1-Mutated Myeloid Neoplasms with <20% Blasts: A Really Distinct Clinico-Pathologic Entity? 3325 88