[HTML][HTML] Molecular subtypes of NPM1 mutations have different clinical profiles, specific patterns of accompanying molecular mutations and varying outcomes in …

T Alpermann, S Schnittger, C Eder, F Dicker… - …, 2016 - ncbi.nlm.nih.gov
T Alpermann, S Schnittger, C Eder, F Dicker, M Meggendorfer, W Kern, C Schmid, C Aul…
Haematologica, 2016ncbi.nlm.nih.gov
NPM1 mutations are important markers for acute myeloid leukemia (AML) and are already
included in the World Health Organization classification of 2008 as indicating a provisional
entity of AML. 1 In addition, it is accepted that NPM1 mutations are prognostically favorable
in the absence of FLT3-ITD mutations. 2-4 Falini and colleagues showed that there are
different types of NPM1 mutations. 5 The “type A” mutation is characterized by insertion of
the four nucleotides thymine, cytosine, thymine and guanine and results in a lengthening of …
NPM1 mutations are important markers for acute myeloid leukemia (AML) and are already included in the World Health Organization classification of 2008 as indicating a provisional entity of AML. 1 In addition, it is accepted that NPM1 mutations are prognostically favorable in the absence of FLT3-ITD mutations. 2-4 Falini and colleagues showed that there are different types of NPM1 mutations. 5 The “type A” mutation is characterized by insertion of the four nucleotides thymine, cytosine, thymine and guanine and results in a lengthening of the protein. In addition, other mutations were detected showing diverse insertions that are all located at the terminal end of exon 12 and were named alphabetically in the order of detection. Although the length of insertion of base pairs is the same in most mutations, the resulting sequence of the amino acids differs. For example, in type A the insertion results in the amino acid leucine, whereas in type B it results in methionine. Some research groups found that patients with these types had different outcomes, whereas other groups did not. 6, 7 Little is known about accompanying mutations besides FLT3-ITD, FLT3-TKD and the absence of MLL-PTD or doublemutated CEBPA mutations. 2, 3, 8 Only FLT3-ITD seems to influence prognosis negatively. 2, 3, 8 Whether the different types of NPM1 mutations, and therefore the different sequences of amino acids, are associated with different cytogenetics, concomitant molecular markers, biological or prognostic profiles remains unclear and is the subject of this study.
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