LAUSR

Deletions in the long arm of chromosome 9, del(9q), are recurrent but rare cytogenetic aberrations in myeloid neoplasms including acute myeloid leukemia (AML), where they were observed with a frequency of ~ 2% (Langabeer et al. 1998; Grimwade et al. 2010; Naarmann-de Vries IS et al. 2018). Del(9q) is considered as marker of intermediate risk according to the MRC classification (Grimwade et al. 2010; Döhner et al. 2010, Grimwade et al. 2016). Cytogenetically, del(9q) can be observed as a sole abnormality or in association with other cytogenetic aberrations. In more detail, a significant association with t(8;21) (q22;q22) (RUNX1-RUNX1T1 rearrangement) and t(15;17) (q24;q21) (PML-RARA rearrangement) was described (Langabeer et al. 1998; Döhner et al. 2010). Moreover, AML with del(9q) was characterized by frequent mutations of NPM1, DNMT3A, CEBPA and WT1, and mutations affecting NPM1 and DNMT3A were exclusively identified in patients with del(9q) as the sole abnormality (Fröhling et al. 2005; Herold et al. 2017). A minimally deleted region of del(9q) was detected in patients with AML that comprises seven genes potentially involved in leukemogenesis (GKAP1, KIF27, C9ORF64, HNRNPK, RMI1, SLC28A3 and NTRK2). Expression of these genes was found to be significantly reduced in patients with del(9q) compared to AML patients with normal karyotype (Naarmann-de Vries IS et al. 2018). Moreover, two genes closely related to the commonly deleted region of del(9q) (TLE1 and TLE4) were identified to contribute to leukemogenesis due to haploinsufficiency in patients with t(8;21)(q22;q22) (Dayyani et al. 2008). In the 2016 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia, del(9q) was excluded as a defining cytogenetic abnormality for AML with myelodysplasia-related changes due to its frequent association with NPM1 and biallelic CEBPA mutations, which themselves define AML subgroups (Arber et al. 2016). Thus, the aim of the present project was the investigation of the frequency of del(9q) in AML and its accompanying molecular and cytogenetic abnormalities and assessment whether or not del(9q) is associated with a myelodysplasia-related mutation profile. We evaluated 9762 AML patients for which bone marrow and/or peripheral blood samples had been sent for diagnosis to the MLL Munich Leukemia Laboratory between 2005 and 2017. Detection of del(9q) was performed using chromosome banding analysis (CBA) as previously described according to standard methods (Schoch et al. 2002). Patients agreed with the use of laboratory data for research studies. The study followed the rules of the Helsinki Declaration. Patients with del(9q) were further analyzed for mutations in NPM1, CEBPA and RUNX1 with amplicon next-sequencing (NGS) to categorize them according to the WHO classification. Patients without a class defining aberration or a complex aberrant karyotype were screened for AMLor MDS-related mutations (ASXL1, BCOR, DNMT3A, EZH2, FLT3-ITD, FLT3-TKD, IDH1, IDH2, KMT2A-PTD, KRAS, NRAS, SF3B1, SRSF2, STAG2, TET2, TP53, U2AF1, WT1 and ZRSR2). The template library was generated with the TruSeq Custom Amplicon Low Input Kit and sequenced with the NextSeq (Illumina, San Diego, CA; sensitivity: 3%). NGS data were analyzed using the Sequence Pilot (version 4.1.1 Build 510 for the Illumina platform, JSI Medical systems, Kippenheim, Germany). SPSS (version 19.0.0) software (IBM Corporation, Armonk, NY) was used for Part of the data was presented at the ASH meeting 2017. The Abstract can be assessed here: http://www.blood journ al.org/conte nt/130/Suppl _1/3925.