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Acute myeloid leukemia with myelodysplasia‐related changes are characterized by a specific molecular pattern with high frequency of ASXL1 mutations
Author(s) -
Devillier Raynier,
GelsiBoyer Véronique,
Brecqueville Mandy,
Carbuccia Nadine,
Murati Anne,
Vey Norbert,
Birnbaum Daniel,
Mozziconacci MarieJoëlle
Publication year - 2012
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.23211
Subject(s) - npm1 , cebpa , myeloid leukemia , medicine , runx1 , incidence (geometry) , idh1 , dysplasia , gastroenterology , myeloid , leukemia , oncology , biology , karyotype , mutation , gene , genetics , chromosome , physics , optics , transcription factor
To determine whether the distinct and heterogeneous WHO category called “AML with myelodysplasia‐related changes” (MRC‐AML), presents specific molecular alterations we searched for mutations in genes known to be mutated in malignant myeloid diseases. In 48 MRC‐AML patients analyzed, we found 17 mutations in ASXL1 (35%), eight in RUNX1 (17%), seven in TET2 (15%), 12 in IDH ( n = 2) or IDH2 ( n = 10) (25%), four in DNMT3A (8%), four in NPM1 (8%), and one in FLT3 (2%). Mutations were more frequent in the intermediate cytogenetic (IC) subgroup of 36 patients than in the unfavorable karyotype subgroup, with an average ratio mutations/patients of 1.36 [0–3] vs. 0.33 [0–2] ( P < 0.001). Then, we compared these 36 patients with IC MRC‐AML with a control panel of 37 no‐MRC‐AML patients, who had both IC and no dysplasia. IC MRC‐AMLs were associated with higher incidence of ASXL1 mutations (47% vs. 0%, P < 0.001) and lower incidence of DNMT3A (6% vs. 38%, P = 0.001), NPM1 (11% vs. 62%, P < 0.001) and FLT3 (3% vs. 49%, P < 0.001) mutations. No difference was found in the incidence of IDH1/2 or TET2 mutations according to the presence of dysplasia. Complete remission rate after intensive treatment was lower in the MRC‐AML group than in the no‐MRC‐AML group (48% vs. 78%, P = 0.023) and in wild type NPM1 patients (50% vs. 84%, P = 0.009). Our study showed that MRC‐AML as defined in the WHO 2008 classification presents a specific mutation pattern characterized by a high frequency of ASXL1 mutations and a low rate of NPM1 , FLT3 , and DNMT3A mutations. Am. J. Hematol. 87:659–662, 2012. © 2012 Wiley Periodicals, Inc.