Characterization of NPM1-mutated AML with a history of myelodysplastic syndromes or myeloproliferative neoplasms.
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Characterization of NPM1-mutated AML with a history of myelodysplastic syndromes or myeloproliferative neoplasms. / Schnittger, S; Bacher, Ulrike; Haferlach, C; Alpermann, T; Dicker, F; Sundermann, J; Kern, W; Haferlach, T.
In: LEUKEMIA, Vol. 25, No. 4, 4, 2011, p. 615-621.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Characterization of NPM1-mutated AML with a history of myelodysplastic syndromes or myeloproliferative neoplasms.
AU - Schnittger, S
AU - Bacher, Ulrike
AU - Haferlach, C
AU - Alpermann, T
AU - Dicker, F
AU - Sundermann, J
AU - Kern, W
AU - Haferlach, T
PY - 2011
Y1 - 2011
N2 - 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 × KITD816V, ETV6-PDGFRB, 2 × JAK2V617F, 2 × 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.
AB - 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 × KITD816V, ETV6-PDGFRB, 2 × JAK2V617F, 2 × 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.
KW - Adult
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - Aged, 80 and over
KW - Cohort Studies
KW - Survival Rate
KW - Disease Progression
KW - Polymerase Chain Reaction
KW - DNA, Neoplasm/genetics
KW - Nuclear Proteins/genetics
KW - Karyotyping
KW - Leukemia, Myeloid, Acute/genetics/mortality
KW - Blast Crisis
KW - Cell Transformation, Neoplastic
KW - Mutation/genetics
KW - Myelodysplastic Syndromes/genetics/mortality
KW - Myeloproliferative Disorders/genetics/mortality
KW - Neoplasms, Second Primary/genetics/mortality
KW - Adult
KW - Humans
KW - Male
KW - Aged
KW - Female
KW - Middle Aged
KW - Aged, 80 and over
KW - Cohort Studies
KW - Survival Rate
KW - Disease Progression
KW - Polymerase Chain Reaction
KW - DNA, Neoplasm/genetics
KW - Nuclear Proteins/genetics
KW - Karyotyping
KW - Leukemia, Myeloid, Acute/genetics/mortality
KW - Blast Crisis
KW - Cell Transformation, Neoplastic
KW - Mutation/genetics
KW - Myelodysplastic Syndromes/genetics/mortality
KW - Myeloproliferative Disorders/genetics/mortality
KW - Neoplasms, Second Primary/genetics/mortality
M3 - SCORING: Journal article
VL - 25
SP - 615
EP - 621
JO - LEUKEMIA
JF - LEUKEMIA
SN - 0887-6924
IS - 4
M1 - 4
ER -
