TY - JOUR
T1 - FLT3 and NPM1 mutations in myelodysplastic syndromes
T2 - Frequency and potential value for predicting progression to acute myeloid leukemia
AU - Bains, Ashish
AU - Luthra, Rajyalakshmi
AU - Medeiros, L Jeffrey
AU - Zuo, Zhuang
PY - 2011/1
Y1 - 2011/1
N2 - We reviewed FLT3 and NPM1 mutation data in a large cohort of patients with myelodysplastic syndrome (MDS). The frequencies of FLT3 and NPM1 mutation were 2.0% and 4.4%, respectively, and mutations were restricted to cases of intermediate- and high-risk MDS. Cytogenetic abnormalities were identified in 46.9% of cases. FLT3 mutations were associated with a complex karyotype (P = .009), whereas NPM1 mutations were associated with a diploid karyotype (P < .001). FLT3 mutation (P < .001) was associated with progression to acute myeloid leukemia (AML), as were a higher bone marrow (BM) blast count (P < .001) and complex cytogenetics (P = .039). No patient with an NPM1 mutation alone had disease that progressed to AML. Cox proportional regression multivariate analysis indicated that FLT3 mutation, NPM1 mutation, complex cytogenetics, BM blast count, pancytopenia, and age were independent factors that correlated with progression-free survival. We conclude that FLT3 and NPM1 mutations are rare in MDS, but assessment of mutation status is potentially useful for predicting progression to AML.
AB - We reviewed FLT3 and NPM1 mutation data in a large cohort of patients with myelodysplastic syndrome (MDS). The frequencies of FLT3 and NPM1 mutation were 2.0% and 4.4%, respectively, and mutations were restricted to cases of intermediate- and high-risk MDS. Cytogenetic abnormalities were identified in 46.9% of cases. FLT3 mutations were associated with a complex karyotype (P = .009), whereas NPM1 mutations were associated with a diploid karyotype (P < .001). FLT3 mutation (P < .001) was associated with progression to acute myeloid leukemia (AML), as were a higher bone marrow (BM) blast count (P < .001) and complex cytogenetics (P = .039). No patient with an NPM1 mutation alone had disease that progressed to AML. Cox proportional regression multivariate analysis indicated that FLT3 mutation, NPM1 mutation, complex cytogenetics, BM blast count, pancytopenia, and age were independent factors that correlated with progression-free survival. We conclude that FLT3 and NPM1 mutations are rare in MDS, but assessment of mutation status is potentially useful for predicting progression to AML.
KW - FLT3
KW - FMS-like tyrosine kinase
KW - Mutation
KW - Myelodysplastic syndromes
KW - NPM1
KW - Nucleophosmin
UR - http://www.scopus.com/inward/record.url?scp=79251500335&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79251500335&partnerID=8YFLogxK
U2 - 10.1309/AJCPEI9XU8PYBCIO
DO - 10.1309/AJCPEI9XU8PYBCIO
M3 - Article
C2 - 21173125
AN - SCOPUS:79251500335
SN - 0002-9173
VL - 135
SP - 62
EP - 69
JO - American journal of clinical pathology
JF - American journal of clinical pathology
IS - 1
ER -