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. 2014 Dec;36(6):656-64.
doi: 10.1111/ijlh.12204. Epub 2014 Mar 25.

Lower frequency of NPM1 and FLT3-ITD mutations in a South African adult de novo AML cohort

R C Marshall  1 , A Tlagadi, M Bronze, V Kana, S Naidoo, T M Wiggill, S C Carmona
Affiliations

Lower frequency of NPM1 and FLT3-ITD mutations in a South African adult de novo AML cohort

R C Marshall et al. Int J Lab Hematol. 2014 Dec.

Abstract

Introduction: Acute myeloid leukemia (AML) is a heterogeneous clonal disorder of hemopoietic progenitor cells diagnosed in individuals of any age, but with a median age of 67 years at presentation in adults. Assessment of the mutation status of nucleophosmin protein-1 (NPM1) and FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) is essential for the prognosis, and treatment of AML.

Methods: A total of 160 de novo AML cases, both cytogenetically normal and abnormal, were analyzed for the presence of NPM1 and FLT3-ITD mutations, and the results assessed in conjunction with epidemiological, clinical, and laboratory findings.

Results: Nucleophosmin protein-1 mutations were found in 7.5%, while FLT3-ITD was present in 12% of these cases. Both of these were lower than expected. The median age at diagnosis of AML was 41 years, and for the FLT3-ITD only cases, median age was 33 years; these ages were younger than expected.

Conclusion: The lower reported frequencies and younger median age at diagnosis of AML and these specific mutations may be contributed to by a number of factors including effects of race on age of presentation, inclusion of patients diagnosed with de novo AML only, and a generally younger median age of the South African population.

Keywords: Acute myeloid leukemia; FLT3-ITD; NPM1; South Africa; frequency.

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Figures

Figure 1
Figure 1
Schematic representation of the distribution of AML patients by mutation sub-category. The patient cohort of 160 de novo AML cases revealed the presence of FLT3-ITD only in 12% of cases and the presence of NPM1-mut only in 7.5% of the cohort. FLT3-ITD positivity was present in 43% of those that were NPM1 mutation positive
Figure 2
Figure 2
Distribution of each mutation category according to age. Those patients with either a single mutation or neither mutation have a peak increase in AML at 20-29 years. Those with neither mutation have a second peak of AML diagnosed at 40-49 years while those with both mutations present concurrently are more likely to be diagnosed with AML later in life with a peak seen at 70-79 years of age
Figure 3
Figure 3
Time to lost to follow up (LTFU) from time of diagnosis (n=130/160). Data source, laboratory information system corporate data warehouse search. A total of 40% of all patients were LTFU by day 40 and 50% of patients were LTFU by day 87. By day 500, 80% of the patients were LTFU, only 5% were followed up for more than 3 years and 8% were confirmed to be alive within the last year
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References

    1. Howlader N, N A, Krapcho M, Garshell J, Neyman N, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Cho H, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA, editors. SEER Cancer Statistics Review, 1975-2010. National Cancer Institute; Bethesda, MD: 2012. [2013 24 March]. Available from: http://seer.cancer.gov/statfacts/html/amyl.html.
    1. Mrózek K, Bloomfield CD. Chromosome aberrations, gene mutations and expression changes, and prognosis in adult acute myeloid leukemia. Hematology Am Soc Hematol Educ Program. 2006:169–77. - PubMed
    1. Grimwade D, Walker H, Oliver F, Wheatley K, Harrison C, Harrison G, et al. The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children’s Leukaemia Working Parties. Blood. 1998;92(7):2322–33. - PubMed
    1. Thiede C, Koch S, Creutzig E, Steudel C, Illmer T, Schaich M, et al. Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML) Blood. 2006;107(10):4011–20. - PubMed
    1. Kottaridis PD, Gale RE, Frew ME, Harrison G, Langabeer SE, Belton AA, et al. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood. 2001;98(6):1752–9. - PubMed

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