Monosomy 7 and activating RAS mutations accompany malignant transformation in patients with congenital neutropenia

Ruby Kalra, David Dale, Melvin Freedman, Mary Ann Bonilla, Mark Weinblatt, Arnold Ganser, Paul Bowman, Sharon Abish, Jack Priest, Ronald S. Oseas, Kristin Olson, Dorothy Paderanga, Kevin Shannon

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Individuals with severe forms of congenital neutropenia suffer from recurrent infections. The therapeutic use of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to increase the neutrophil count is associated with fewer infections and an improved quality of life. However, the long-term effects of this new therapy are largely unknown. In particular, it is unclear if myeloid leukemia, a known complication of some forms of congenital neutropenia, will occur with increased frequency among patients who receive long-term treatment with hematopoietic growth factors. We report 13 patients with congenital disorders of myelopoiesis who developed leukemic transformation with either myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) and 1 who acquired a clonal cytogenetic abnormality without evidence of MDS or AML while receiving rhG-CSF. The bone marrows of 10 patients showed monosomy 7 and 5 had activating RAS mutations. These abnormalities were not detected in pretreatment bone marrows and cessation of rhG-CSF was not associated with either clinical improvement or cytogenetic remission. We conclude that patients with severe forms of congenital neutropenia are at relatively high risk of developing MDS and AML. The occurrence of monosomy 7 and RAS mutations in these cases suggests that the myeloid progenitors of some patients are genetically predisposed to malignant transformation. The relationship between therapeutic rhG-CSF and leukemogenesis in patients with severe chronic neutropenia is unclear.

Original languageEnglish
Pages (from-to)4579-4586
Number of pages8
Issue number12
StatePublished - 15 Dec 1995


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