Journal
LEUKEMIA
Volume 25, Issue 4, Pages 615-621Publisher
SPRINGERNATURE
DOI: 10.1038/leu.2010.299
Keywords
NPM1 mutations; secondary acute myeloid leukemia; leukemogenesis; myelodysplastic syndrome; myeloproliferative neoplasms
Categories
Ask authors/readers for more resources
The role of the nucleophosmin (NPM1) mutations in de novo acute myeloid leukemia (AML) is well analyzed, but the impact in secondary AML (s-AML) following myelodysplastic syndromes (MDS) or transformed myeloproliferative neoplasms (MPNs) remains unclear. We investigated 350 patients-283 s-AML after MDS and 67 transformed MPNs-for NPM1mut. NPM1mut was detected in 43/350 patients (12.3%) at diagnosis of s-AML (transformed MDS: 37/283; 13.1%; transformed MPNs: 6/67; 9.0%). Cytogenetic alterations were present in 12/40 cases (30.0%) with available karyotypes. Additional molecular mutations were found in 23/43 NPM1mut s-AML after MDS (53.5%) and in transformed MPN in 18/37 (48.6%): FLT3-ITD: 14/37 (37.8%); FLT3-TKD: 3/28 (10.7%); NRASmut: 4/37 (10.8%), RUNX1mut: 1/16 (6.3%). In NPM1mut-transformed MPNs, five out of six cases showed 1-2 additional molecular mutations (2 x KITD816V, ETV6-PDGFRB, 2 x JAK2V617F, 2 x FLT3-ITD). Backtracking of nine of these cases by quantitative real time PCR showed the NPM1mut already at diagnosis of MDS/MPN, at variable levels and up to 14 months before diagnosis of AML, and at transformation often being preceded or accompanied by other genetic alterations. Thus, NPM1 mutations are involved in the transformation from MDS to AML or MPN to blast phase in single cases, which should be further confirmed in larger studies. Leukemia (2011) 25, 615-621; doi:10.1038/leu.2010.299; published online 14 January 2011
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available