T618I-Mutated Colony Stimulating Factor 3 Receptor in Chronic Neutrophilic Leukemia and Chronic Myelomonocytic Leukemia Patients who Underwent Allogeneic Stem Cell Transplantation

Dear Editor Recently, the mutations within the colony-stimulating factor 3 receptor gene (CSF3R) have been reported as a specific marker of chronic neutrophilic leukemia (CNL) and atypical CML (aCML) [1, 2]. The current WHO system classifies CNL as a BCR-ABL1negative myeloproliferative neoplasm (MPN). However, in routine clinical practice, it is difficult to clearly distinguish CNL from aCML, chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia, and MDS/MPN, unclassifiable under the MDS/MPN umbrella [3]. Therefore, molecular characteristics (e.g., CSF3R mutation) need to be included in the WHO diagnostic criteria. Here, we describe two CSF3R T618I-mutated patients with CNL and CMML, respectively, who underwent allogeneic stem cell transplantation (allo-SCT). A 40-yr-old man presented in 2012 with marked neutrophilia. His total white blood cell count was 77.24×10/L with a differential of 80% neutrophils, 3% band forms, 3% metamyelocytes, 1% myelocytes, 1% promyelocytes, 1% blasts, 3% lymphocytes, and 10% monocytes (Fig. 1A). He had a 23-cm splenomegaly. His bone marrow (BM) aspirate and biopsy showed hypercellularity with granulocytic hyperplasia (Fig. 1B), with a normal karyotype and no evidence of BCR-ABL1, PDGFRA, or PDGFRB rearrangement when examined by FISH. Molecular studies demonstrated the absence of JAK2 V617F and BCR-ABL1 transcripts. CNL was diagnosed in accordance with the WHO diagnostic criteria, and the patient was treated with hydroxyurea. However, his neutrophilia persisted in the peripheral blood as anemia and thrombocytopenia developed. Repeated BM examinations showed hypercellular BM with granulocytic hyperplasia and decreased megakaryocytes, and a clonal chromosomal abnormality of 46,XY,der(18:21)(q10;q10),+21[7]/47,+21[5]/46 ,XY[8]. The CSF3R T618I mutation was detected (Fig. 2A). He then underwent myeloablative allo-SCT, using cells from an unrelated donor. At day 35 following the allo-SCT, BM examination showed 70% cellularity with 100% donor chimerism. The T618I mutation was not detected in the BM aspirates through sequencing (Fig. 2C). A 60-yr-old man who presented with recurrent purpura on his extremities was referred to our hospital. He had constitutional symptoms including fatigue and weight loss. A computed tomog-