Germline CSF3R Variant in Chronic Myelomonocytic Leukemia: Linking Genetic Predisposition to Uncommon Hemorrhagic Symptoms

Chronic myelomonocytic leukemia (CMML) is a hematological neoplasm characterized by monocytosis, splenomegaly, thrombocytopenia, and anemia. Moreover, it is associated with SRSF2 mutations and, rarely, with CSF3R variants. We present the case of an 84-year-old patient with persistent anemia and monocytosis. Due to the presence of dysmorphic granulocytes, monocyte atypia, and myeloid precursors in the peripheral blood cells, the patient was subjected to a bone marrow examination. The diagnosis was consistent with CMML type 2. The Hemocoagulative test showed an increase in fibrinolysis markers. Next-generation targeted sequencing showed TET2 and SRSF2 mutations, along with an unexpected CSF3R germline missense variant, rarely encountered in CMML. The patient started Azacitidine treatment and achieved normal hemostatic process values. In conclusion, we identified a heterozygous germline mutation that, together with TET2 and SRSF2 variants, was responsible for the hemorrhagic manifestation.

Automated summary

Chronic myelomonocytic leukemia (CMML) is a hematological neoplasm characterized by monocytosis, splenomegaly, thrombocytopenia, and anemia. This study presented a case of CMML-2 with TET2, SRSF2, and a rare CSF3R germline mutation. The patient achieved normalization of the hemostatic process after treatment with Azacitidine.