Langabeer, Stephen E.

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EXCLI Journal 2019;18:256-258 – ISSN 1611-2156 Received: March 5, 2019, accepted: April 4, 2019, published: May 16, 2019   256 Letter to the editor: THE MUTATIONAL LANDSCAPE OF ATYPICAL CHRONIC  MYELOID LEUKEMIA  Stephen E. Langabeer  Cancer Molecular Diagnostics, St. James’s Hospital, Dublin, Ireland E-mail: slangabeer@stjames.ie, Phone: +353-1-4103576, Fax: +353-1-4103513   http://dx.doi.org/10.17179/excli2019-1246  This is an Open Access article distributed under the terms of the Creative Commons Attribution License  (http://creativecommons.org/licenses/by/4.0/).   Dear Editor, Atypical chronic myeloid leukemia (aCML) is a rare haematological malignancy classified as a myelodysplastic/myeloproliferative neoplasm (MDS/MPN). Diagnostic criteria include leucocytosis with left shift, dysgranulopoiesis, minimal basophila and monocytosis, a hyper-cellular bone marrow, less than 20 % myeloblasts in the blood or bone marrow, and absence of the distinct molecular abnormalities of classical MPN (Arber et al., 2016). Until recently, treat-ment for aCML has been largely based on those agents used for either MDS or MPN type with varying degrees of success (Gotlib, 2017). While haematopoietic allogeneic stem cell trans-plantation remains the only curative therapy, it is limited to those aCML patients eligible for such a procedure (Onida et al., 2017). In other myeloid malignancies, targeted sequencing has identified recurrently mutated genes providing both insight into disease pathogenesis and helped to unmask therapeutically actionable molecular abnormalities.  Several studies have investigated the mutation profile of sizeable cohorts of aCML patients in chronic and blast crisis phases by targeted sequencing of recurrently mutated genes of mye-loid malignancies. However, in order to comprehensively survey the current mutational land-scape of aCML, these studies together with smaller series and case reports adopting such tar-geted sequencing approaches in the literature, are summarised in Figure 1. Caveats include the use of evolving classification criteria for aCML, possible duplication of patients in two or more studies, and differences in the genes covered by independent targeted sequencing approaches. From this summary, the most frequently mutated genes in aCML patients appear to be ASXL1, NRAS, SETBP1, SRSF2 and TET2. In addition to broad cytoreductive and supportive measures (Schwartz and Mascarenhas, 2019), clinical responses with inhibitors of mutated NRAS and FLT3 have been observed in single cases validating this individualized approach (Khanna et al., 2015; Langabeer et al., 2017). Due to the lack of a standard of care combined with the clinical and genetic heterogeneity of this malignancy, a personalized prognostic and therapeutic direction to aCML management is anticipated, facilitated by the progressively fundamental role of targeted mutation profiling.  Conflict of interest The author declares no conflict of interest. EXCLI Journal 2019;18:256-258 – ISSN 1611-2156 Received: March 5, 2019, accepted: April 4, 2019, published: May 16, 2019   257  Study Piazza et al., 2013 Meggendorfer et al., 2013 Meggendorfer et al., 2014 Gambacorti-Passerini et al., 2015 Khanna et al., 2015 Patnaik et al., 2017 Langabeer et al., 2017 Gilioli et al., 2018 Gurnari et al., 2018 Faisal et al., 2019 Patients n=70 n=60 n=58 n=15 n=1 n=25 n=1 n=1 n=1 n=29 ASXL1                     BRAF                              CBL                     CEBPA                     CSF3R                     DNMT3A                              EED                     ETNK1                     EZH2                     FLT3                     IDH1                              IDH2                     JAK2                     JARID2                     KIT                              KRAS                     MPL                     NRAS                     PTPN11                     RUNX1                     SETBP1                     SF3B1                     SRSF2                     SUZ12                     TET2                     TP53                              U2AF1                     WT1                     ZRSR2                     Figure 1: Mutated myeloid malignancy-associated genes (red shading) by targeted sequencing in aCML patientsEXCLI Journal 2019;18:256-258 – ISSN 1611-2156 Received: March 5, 2019, accepted: April 4, 2019, published: May 16, 2019   258 REFERENCES Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. 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The mutational landscape of atypical chronic myeloid leukemia

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