The detection of SRSF2 mutations in routinely processed bone marrow biopsies is useful in the diagnosis of chronic myelomonocytic leukemia

Diagnosis of chronic myelomonocytic leukemia (CMML) is based on a combination of clinical, laboratory, and morphological parameters, including persistent peripheral blood monocytosis. Recently, mutations of serine/arginine-rich splicing factor 2 (SRSF2) have been identified in 40% to 50% of CivIMLs and occasionally in other myeloid disorders. In this study, we established a robust assay for the detection of SRSF2 mutations in decalcified, paraffin-embedded bone marrow (BM) biopsies and investigated its diagnostic utility. BM biopsies of 78 patients with myeloid neoplasms, including 36 CMMLs, 22 myelodysplastic syndromes (MDS), and 20 Ph- myeloproliferative neoplasms (MPN) were analyzed. The region around hot spot P95 in exon 1 of SRSF2 was amplified and bidirectionally sequenced. In addition, a restriction fragment length polymorphism analysis was established. The JAK2 V617F mutation was investigated by allele-specific polymerase chain reaction. SRSF2 mutations were identified in 16 (44%) of 36 CMMLs, including 1 of 3 cases with associated systemic mastocytosis, 4(20%) of 20 Ph MPN, and 1 (4.5%) of 22 MDS. Restriction fragment length polymorphism analysis detected all mutations with the exception of a single P95A. Of note, 2 cases of JAK2 V617F+ primary myelofibrosis with SRSF2 mutation initially were diagnosed as CMML based on significant peripheral blood monocytosis. In CMML, no correlation with histopathology and/or clinical parameters was observed, but SRSF2 mutations were associated with normal karyotype (P <.001). In summary, SRSF2 mutations are frequent in CMML and a useful diagnostic feature demonstrable in BM biopsies, allowing a definitive diagnosis for cases with minimal dysplasia and normal karyotype. The role of SRSF2 mutations in cases with hybrid features between primary myelofibrosis and CMML needs further investigation. (C) 2014 Elsevier Inc. All rights reserved.