Minimal residual disease detection in acute myeloid leukemia by mutant nucleophosmin (NPM1): comparison with WT1 gene expression.
BACKGROUND
Molecular analysis of minimal residual disease is only applicable in acute myeloblastic leukemia (AML) patients with genetic markers (20-30%). This study analyzes the feasibility of the real-time quantitative polymerase chain reaction (RQ-PCR) assay to detect mutant nucleophosmin (NPM1) during follow-up in AML patients. Moreover, we compare the NPM1 results with those of WT1 expression to MRD assessment.


METHODS
The study includes 97 samples from 24 AML patients with type A NPM1 mutation at diagnosis. MRD was evaluated simultaneous by RQ-PCR assay to detect NPM1-mutated and WT1 expression.


RESULTS
The expression levels of WT1 and NPM1 in 93 paired samples showed a strong positive correlation (r=0.81; p<0.0001). However, the kinetics of disappearance were different, WT1 decreased rapidly after induction but maintained these residual levels after treatment in patients in complete remission, whereas NPM1 experienced a mild reduction after induction but was undetectable in long survivor patients.


CONCLUSIONS
This study shows the feasibility of the RQ-PCR assay to monitor MRD in AML patients carrying NPM1 mutations and its advantage over RQ-PCR assay for WT1. Owing to NPM1-mutated is specific of leukemic cells and shows higher levels at presentation.
Barragan
Eva
E
Department of Medical Pathology, Hospital Universitario La Fe Valencia, Spain. barragan_eva@gva.es
Pajuelo
Juan C
JC
Ballester
Sandra
S
Fuster
Oscar
O
Cervera
Jose
J
Moscardo
Federico
F
Senent
Leonor
L
Such
Esperanza
E
Sanz
Miguel A
MA
Bolufer
Pascual
P
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D016162:Genes, Wilms Tumor; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D016133:Polymerase Chain Reaction / Q000379:methods; D012008:Recurrence; D012074:Remission Induction; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013997:Time Factors
C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin