Granulocyte colony-stimulating factor receptor mutations in a patient with acute lymphoblastic leukemia secondary to severe congenital neutropenia

Granulocyte colony-stimulating factor receptor mutations in a patient with acute lymphoblastic leukemia secondary to severe congenital neutropeniaSevere congenital neutropenia (CN) is a group of hematopoietic disorders with variable recessive inheritance characterized by absolute neutropenia due to a maturation arrest of myeloid progenitor cells.] Patients with acquired nonsense mutations in the granulocyte colony-stimulating factor (G-CSF) receptor gene leading to the truncation of the membrane-distal region of the receptor have a high risk of leukemic transformation. 2-3So far, none of the known patients with CN have developed a secondary acute lymphocytic leukemia (ALL).Here we report on a 14-year-old girl with CN who developed a secondary pre-B acute lymphoblastic leukemia (pre-B ALL).CN was diagnosed at the age of 4 months, and she was started on r-metHuG-CSF (10 g/kg/d) at age 9, followed by a prompt increase in neutrophil counts.Yearly bone marrow investigations were consistent with CN (Figure 1A).At age 13, she developed an ALL with more than 90% lymphoblasts in the bone marrow (Figure 1B).The immunophenotype of the blasts as judged from flow cytometry was in accordance with a pre-B ALL, coexpressing myeloid markers: CD19 (69%), CD20 (57%), CD45 (68%), CD34 (84%), HLA-DR (91%), CD13 (67%), CD24 (22%), CD33 (29%), CD10 (Ͻ 1%).Intracellular staining demonstrated TdT (67%), CD79a (20%), immunoglobulin M ( chain)(20%),