Chronic myelomonocytic leukemia genomic signature correlates with the degree of bone marrow fibrosis: A single-institutional retrospective study.

Abstract

7559 Background: Chronic myelomonocytic leukemia (CMML) has features of both a myeloproliferative neoplasm and a myelodysplastic syndrome. The median overall survival (OS) in most series is 20-40 months. CMML is a relatively rare entity, and there is limited understanding of prognostic molecular markers. CMML associated with bone marrow fibrosis grade 1, appear to have shorter progression free survival. In this study we investigated the correlation of mutations with bone marrow reticulin fibrosis in patients with CMML. Methods: We investigated a cohort of 41 consecutive patients diagnosed with CMML 0, 1, 2, and CMML-AML from 2014 to 2019 at our institute. The median age of 41 patients was 68 years (range, 34-82). 27% were females and 73% were males. This cohort consists of 8 (20%) patients with CMML0, 19 (46%) with CMML1, 8 (20%) with CMML2 and 6 (15%) with CMML-AML. Genomic DNA was extracted from the bone marrow aspirates and targeted mutation NGS libraries were prepared from 200 ng of genomic DNA using the SureSelect target enrichment system (Agilent Technologies Inc.). The gene panel consists of 73 genes focused on myeloid neoplasms. The data were curated on the basis of our molecular pathology and national databases. Additionally, clinical data and bone marrow (BM) reticulin fibrosis grades (n = 27 available) were retrieved from the patient’s medical record. Results: The mutational profile frequency in our cohort showed that the most common mutations were TET2 (31%), ASXL1 (31%), and SRSF2 (23%), with frequencies very similar to those reported in the literature. Of the 27 cases with an available reticulin stain, only low grade fibrosis (MF-0, n = 18. MF-1, n = 9) were identified in our cohort. The frequencies of mutations in ASXL1, U2AF1, TP53, JAK2 and RUNX1, positively correlated with low grade fibrosis (MF-1). Additionally, patients with higher frequencies of SRSF2, TET2, and SETBP1 mutations showed no fibrosis (MF-0). Conclusions: This study is the first to correlate the degree of fibrosis with the frequency of mutations in CMML. We found similar mutations spectrum reported in the literature in patients with CMML. The mutational profile associated with CMML cases appears to affect the degree of the bone marrow fibrosis at the time of diagnosis.