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

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus

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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Figure 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.

Mentions: The NPM1-mutA quantitation results obtained at diagnosis and at 28 days after chemotherapy were assessed in each patient and analyzed in relation to the clinical condition of the patient. In addition, for each patient, the BM blast counts measured at diagnosis and at 28 days after chemotherapy were correlated with their NPM1-mutA quantity. These results are summarized in Table 1. For the five patients who experienced relapse during follow-up, NPM1-mutA mRNA levels at each follow-up time point before the relapse were assessed, and compared with the patient's clinical condition. These results are illustrated in Fig. 1.


Correlation of NPM1 Type A Mutation Burden With Clinical Status and Outcomes in Acute Myeloid Leukemia Patients With Mutated NPM1 Type A
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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4940481&req=5

Figure 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.
Mentions: The NPM1-mutA quantitation results obtained at diagnosis and at 28 days after chemotherapy were assessed in each patient and analyzed in relation to the clinical condition of the patient. In addition, for each patient, the BM blast counts measured at diagnosis and at 28 days after chemotherapy were correlated with their NPM1-mutA quantity. These results are summarized in Table 1. For the five patients who experienced relapse during follow-up, NPM1-mutA mRNA levels at each follow-up time point before the relapse were assessed, and compared with the patient's clinical condition. These results are illustrated in Fig. 1.

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus