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Clinical implications of ELA2 ‐, HAX1 ‐, and G‐CSF‐receptor ( CSF3R ) mutations in severe congenital neutropenia
Author(s) -
Zeidler Cornelia,
Germeshausen Manuela,
Klein Christoph,
Welte Karl
Publication year - 2009
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2008.07425.x
Subject(s) - congenital neutropenia , promyelocyte , neutropenia , medicine , leukemia , immunology , preleukemia , myeloid leukemia , myelopoiesis , genetic heterogeneity , myeloid , compound heterozygosity , mutation , phenotype , cancer research , haematopoiesis , biology , genetics , gene , stem cell , chemotherapy
Summary Congenital Neutropenia (CN) is a heterogeneous bone marrow failure syndrome characterized by a maturation arrest of myelopoiesis at the level of the promyelocyte/myelocyte stage with peripheral blood absolute neutrophil counts below 0·5 × 10 9 /l. There are two major subtypes of CN as judged by inheritance: an autosomal dominant subtype, e.g. defined by neutrophil elastase mutations (approximately 60% of patients) and an autosomal recessive subtype (approximately 30% of patients), both presenting with the same clinical and morphological phenotype. Different mutations have been described (e.g. HAX1 , p14 etc) in autosomal recessive CN, with HAX1 mutations in the majority of these patients. CN in common is considered as a preleukemic syndrome, since the cumulative incidence for leukemia is more than 25% after 20 years of observation. Leukemias occur in both, the autosomal dominant and recessive subtypes of CN. The individual risk for each genetic subtype needs to be further evaluated. Numbers of patients tested for the underlying genetic defect are still limited. Acquired G‐CSFR ( CSF3R ) mutations are detected in approximately 80% of CN patients who developed acute myeloid leukemia independent of the ELA2 or HAX1 genetic subtype, suggesting that these mutations are involved in leukemogenesis. As the majority of patients benefit from G‐CSF administration, HSCT should be restricted to non‐responders and patients with leukaemic transformation.