Ann Lab Med.  2016 Sep;36(5):399-404. 10.3343/alm.2016.36.5.399.

Correlation of NPM1 Type A Mutation Burden With Clinical Status and Outcomes in Acute Myeloid Leukemia Patients With Mutated NPM1 Type A

• Jo SY
• Park SH
• Kim IS
• Yi J
• Kim HH
• Chang CL
• Lee EY
• Cho YU
• Jang S
• Park CJ
• Chi HS

• KMID: 2373568
• DOI: http://doi.org/10.3343/alm.2016.36.5.399

Abstract

BACKGROUND
Nucleophosmin gene (NPM1) mutation may be a good molecular marker for assessing the clinical status and predicting the outcomes in AML patients. We evaluated the applicability of NPM1 type A mutation (NPM1-mutA) quantitation for this purpose.
METHODS
Twenty-seven AML patients with normal karyotype but bearing the mutated NPM1 were enrolled in the study, and real-time quantitative PCR of NPM1-mutA was performed on 93 bone marrow (BM) samples (27 samples at diagnosis and 56 at follow-up). The NPM1-mutA allele burdens (represented as the NPM1-mutA/Abelson gene (ABL) ratio) at diagnosis and at follow-up were compared.
RESULTS
The median NPM1-mutA/ABL ratio was 1.3287 at diagnosis and 0.092 at 28 days after chemotherapy, corresponding to a median log10 reduction of 1.7061. Significant correlations were observed between BM blast counts and NPM1-mutA quantitation results measured at diagnosis (γ=0.5885, P=0.0012) and after chemotherapy (γ=0.5106, P=0.0065). Total 16 patients achieved morphologic complete remission at 28 days after chemotherapy, and 14 (87.5%) patients showed a >3 log10 reduction of the NPM1-mutA/ABL ratio. The NPM1-mutA allele was detected in each of five patients who had relapsed, giving a median increase of 0.91-fold of the NPM1-mutA/ABL ratio at relapse over that at diagnosis.
CONCLUSIONS
The NPM1-mutA quantitation results corresponded to BM assessment results with high stability at relapse, and could predict patient outcomes. Quantitation of the NPM1-mutA burden at follow-up would be useful in the management of AML patients harboring this gene mutation.

Keyword

AML; NPM1 type A mutation; Quantitation; Real-time PCR; Monitoring

MeSH Terms

Antineoplastic Agents/therapeutic use
Bone Marrow/metabolism/pathology
Cytarabine/therapeutic use
Daunorubicin
Humans
Karyotype
Leukemia, Myeloid, Acute/drug therapy/genetics/*pathology
Mutation
Nuclear Proteins/*genetics/metabolism
Real-Time Polymerase Chain Reaction
Recurrence
Remission Induction
Retrospective Studies
Sequence Analysis, DNA
fms-Like Tyrosine Kinase 3/genetics
Antineoplastic Agents
Cytarabine
Daunorubicin
Nuclear Proteins
fms-Like Tyrosine Kinase 3

Figure

• 

  Fig. 1 Quantitation of the NPM1 type A mutation in bone marrow aspirates from five relapsed AML patients, obtained at diagnosis and at each follow-up day. The results for each patient are represented with different colored lines (dark blue, Patient No. 5; red, Patient No. 6; green, Patient No. 8; light blue, Patient No. 23; purple, Patient No. 27, respectively as in Table 1).Abbreviations: NPM1-mutA, nucleophosmin mutation type A; ABL, the Abelson gene; CR, complete remission; Hypo, hypocellular marrow; BMT, bone marrow transplantation.

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