Mutations in AML with a normal karyotype: NPM1 and FLT3-ITD, ready to use as a key prognosticator?

which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Two well defined mutations, including the NPM1 and CCAAT/enhancer-binding protein-alpha (CEBPA) genes, are generally accepted as a better prognosis in AML [1]. NPM1, one of frequent mutations in AML, have been described in association with several clinical features, including a normal karyotype and a significantly higher long-term survival benefit compared to those patients who are having other mutations. However, there have been many reports, although they are not confirmative yet, about the role of this specific mutation whether it is really positive or negative influential to the response after chemotherapy and/or hema-topoietic stem cell transplantation (HSCT). Is the mutational state of NPM1 alone or in combination with other defined mutations in AML matter when we treat the patients in any manner, i.e. either use of conventional chemothera-peutic agents or novel developmental agents introduced recently or even combination of sequential chemotherapies followed by HSCT? There is no clear answer yet unfortunately. Furthermore, some studies showed that although NPM1 mutation was a favorable factor for achieving complete remission (CR), it was even associated with a higher relapse rate and poorer disease-free survival (DFS) [2]. What is more interesting, the mutational state of NPM1 alone had no significant effect on DFS and could not be a favorable prognostic factor for AML [3, 4]. Finally, no clinical significance for this mutation with respect to overall survival (OS) was described in any of these reports. Also, there is another recent Korean report that non-A subtype NPM1 mutation predicts poor clinical outcome in de novo adult AML [5]. Because of the large variability of gene mutations or the heterogeneity of AML, it is basically understood as a very complex disease entity having diverse prognosticators. Therefore, many combinations of molecular markers in association with treatment outcome of AML have been introduced recently. Although there is not enough evidence to insist of positive impact on clinical outcome of NPM1 mutation, it seems like that patients with isolated NPM1 mutation (NPM1mut) generally had a better outcome in terms of either OS or DFS as compared to the group of NPM1mut+/FLT3-ITD+ patients [6, 7]. In contrast, most studies have reported that FLT3-ITD+ is an independent poor prognostic factor contributing to an increased risk of induction failure and finally poor survival. Based on these concepts, Kim et al. [8] showed in previous issue …