Mutations of the CCAAT/enhancer binding protein alpha (CEBPA) gene have been associated with a favorable outcome in patients with acute myeloid leukemia (AML), but mainly in those with a normal karyotype. Here, we analyzed the impact of associated cytogenetic abnormalities or bad-prognosis fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) in 53 patients with CEBPA ؉ de novo AML treated in the Acute Leukemia French Association trials. We found that only those with a normal karyotype and no FLT3-ITD displayed the expected favorable outcome. In this context, relapsefree, disease-free, and overall survival were significantly longer than in corresponding patients without the CEBPA mutation (P ‫؍‬ .035, .016, and .047, respectively). This was not observed in the context of an abnormal karyotype or associated FLT3-ITD. Furthermore, after adjustment on age, trial, and mutation type, these features were independently predictive of shorter overall survival in the subset of patients with CEBPA ؉ AML (multivariate hazard ratio ‫؍‬ 2.7; 95% confidence interval, 1.08-6.7; and 2.9; 95% confidence interval, 1. IntroductionThe prognosis of patients with acute myeloid leukemia (AML) has been deeply refined because of the impact of new molecular markers. If standard cytogenetics remains a strong factor for both complete remission (CR) achievement and relapse, several gene mutations have been described and demonstrated as significantly influencing the outcome of these patients. 1 In this new context, most cooperative groups recommend to screen for some gene mutations at diagnosis, including the fms-like tyrosine kinase 3 (FLT3), the nucleophosmine (NPM1), and the CCAAT/enhancer binding protein alpha (CEBPA) genes. 2 We have previously reported that CEBPA mutations are associated with a favorable outcome in younger patients with newly diagnosed AML. 3 This was confirmed by other groups, but mainly in patients with cytogenetically normal (CN) AML. [4][5][6][7] The issue of whether this favorable impact is still observed in patients with AML carrying cytogenetic abnormalities remains open. Another open issue is to determine whether cooperating bad-prognosis FLT3 internal tandem duplication (FLT3-ITD) may alter the prognosis of CEBPA mutated (CEBPA ϩ ) AML. 3,5,7 Finally, it has been recently reported that only CEBPA double mutations, but not single, might be associated with a good outcome. 8 In the present study, we thus analyzed the role of these factors in 53 patients with CEBPA ϩ AML treated in Acute Leukemia French Association (ALFA) trials. MethodsA total of 1529 patients (15-70 years of age) with newly diagnosed AML entered the ALFA-9000, ALFA-9801, and ALFA-9802 trials between 1990 and 2006. Trial designs have been already reported. [9][10][11] Briefly, the first ALFA-9000 trial demonstrated the superiority of an intensified timedsequential over a standard (3 ϩ 7) induction in terms of relapse incidence in the subgroup of patients 50 years of age or younger. 9 From 1998, these younger patients were thus treated...

FIP1L1-PDGFRA-positive myeloid neoplasm with eosinophilia (F/P+ MN-eo) is a rare disease: robust epidemiological data are lacking and reported issues are scarce, of low sample-size and limited follow-up. Imatinib mesylate (IM) is highly efficient but no predictive factor of relapse after discontinuation has yet been identified. One hundred and fifty-one patients with F/P+ MN-eo (143 males; mean age at diagnosis 49 years; mean annual incidence: 0.18 case per million population) were included in this retrospective nationwide study involving all French laboratories who perform the search of F/P fusion gene (study period: 2003-2019). The main organs involved included the spleen (44%), skin (32%), lungs (30%), heart (19%) and central nervous system (9%). Serum vitamin

Classical hairy cell leukemia (HCL-c) is a rare lymphoid neoplasm. BRAFV600E mutation, detected in more than 80% of the cases, is described as a driver mutation, but additional genetic abnormalities appear to be necessary for the disease progression. For cases of HCL-c harboring a wild-type BRAF gene, the differential diagnosis of the variant form of HCL (HCL-v) or splenic diffuse red pulp lymphoma (SDRPL) is complex. We selected a panel of 21 relevant genes based on a literature review of whole exome sequencing studies (BRAF, MAP2K1, DUSP2, MAPK15, ARID1A, ARID1B, EZH2, KDM6A, CREBBP, TP53, CDKN1B, XPO1, KLF2, CXCR4, NOTH1, NOTCH2, MYD88, ANXA1, U2AF1, BCOR, and ABCA8). We analyzed 20 HCL-c and 4 HCL-v patients. The analysis of diagnostic samples mutations in BRAF (n = 18), KLF2 (n = 4), MAP2K1 (n = 3), KDM6A (n = 2), CDKN1B (n = 2), ARID1A (n = 2), CREBBP (n = 2) NOTCH1 (n = 1) and ARID1B (n = 1). BRAFV600E was found in 90% (18/20) of HCL-c patients. In HCL-c patients with BRAFV600E, other mutations were found in 33% (6/18) of cases. All 4 HCL-v patients had mutations in epigenetic regulatory genes: KDM6A (n = 2), CREBBP (n = 1) or ARID1A (n = 1). The analysis of sequential samples (at diagnosis and relapse) from 5 patients (2 HCL-c and 3 HCL-v), showed the presence of 2 new subclonal mutations (BCORE1430X and XPO1E571K) in one patient and variations of the mutated allele frequency in 2 other cases. In the HCL-v disease, we described new mutations targeting KDM6A that encode a lysine demethylase protein. This opens new perspectives for personalized medicine for this group of patients.