PB2077 THE CSF3R T618I MUTATION IS HIGHLY PREVALENT AMONG ATYPICAL CHRONIC MYELOID LEUKEMIA PATIENTS FROM SOUTH KOREA: A SINGLE CENTER EXPERIENCE
Authors: S. Y. Kim, I.‐C. Song, J. Kim, M. Koo, Y. Park, H. Kim, Q. Choi, J. Kim, D.‐Y. Jo, G. C. Kwon, S. H. Koo
Journal: HemaSphere (2019)

Background: The mutations in colony‐stimulating factor 3 receptor gene ( CSF3R ) have been known as a hallmark of chronic neutrophilic leukemia (CNL). CSF3R mutations were also found in some atypical chronic myeloid leukemia (aCML) patients, however, recent studies of aCML cohort have shown that CSF3R mutations are rare in aCML. After the starting of CSF3R testing, we have encountered several aCML patients with CSF3R T618I mutations. Hear, we report our series of CSF3R ‐mutated aCML patients. Aims: The aim of this study is to demonstrate molecular, hematologic and clinical characteristics of CSF3R ‐mutated aCML patients. Methods We included 5 newly‐diagnosed aCML patients who were underwent bone marrow (BM) examination and CSF3R gene testing during 2016 to 2018. Sanger sequencing was performed for exon 14 of CSF3R gene. For patients with CSF3R T618I mutation and several other patients with myeloid malignancies, next‐generation sequencing (NGS)‐based gene panel testing was performed. During follow‐up of the patients, CSF3R T618I mutant allele‐burden was analyzed by pyrosequencing. Results: From 2016 to 2018, a total of 1228 patients underwent bone marrow examination for the first hematologic diagnosis. Among them, 5 patients were diagnosed with aCML. The number of cases with other myeloid malignancies were as follows: 137 acute myeloid leukemia (AML), 89 myeloproliferative neoplasm (MPN), 74 myelodysplastic syndrome (MDS), 45 chronic myeloid leukemia, BCR‐ABL1 ‐positive (CML), and 15 chronic myelomonocytic leukemia (CMML). Therefore, the incidence of aCML was about 7 cases for every 100 MDS cases, and 11 cases for every 100 CML cases. There was no newly‐diagnosed CNL cases during the study period. Among 5 aCML patients, 4 patients (80%) had CSF3R T618I mutations. Among 224 patients with other myeloid malignancies for whom gene panel testing was performed, there were 2 AML patients with CSF3R T640 N mutations, one of them also had CSF3R exon 17 frameshift mutation. The aCML patients were all males and three them were &gt; 60 years old and two patients were in their 30s. The median leukocyte counts were 56.24 ×10 9 /L (range, 30.95‐104.5 ×10 9 /L). All the patients presented ≥ 10% of neutrophil precursors in the peripheral blood (PB). Three patients had blasts (3% &gt; 10%) in PB, and all of them had CSF3R T618I mutations. In the BM, all the patients presented granulocytic hyperplasia, 80% to 90% of BM cellularity, and dysgranulopoiesis. Mutations in SETBP1 , SRSF2 , TET2 , ASXL1 , and STAG2 were also found in patients with CSF3R T618I mutations. Three patients were treated with allogenic stem cell transplantation, and 1 patient presented relapse with 45% of CSF3R T618I mutant allele burden in PB. Summary/Conclusion: In our series of aCML patients, the frequency of CSF3R T618I mutation was higher as compared with previous data. In our study, aCML patients could be clearly differentiated from CNL by hematologic characteristics including blasts in PB and dysgranulopoiesis. Our observation might reflect ethnic or geographical differences in the molecular pathogenesis of these rare myeloid malignancies.