Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Chronic Neutrophilic Leukemia (CNL) [D47.1]

OMIM numbers: - , 612990 (ASXL1), 138971 (CSF3R), 611060 (SETBP1), 130130 (ELANE)

Dipl.-Ing. (FH) Tanja Hinrichsen

Scientific Background

Cases are rarely described (2008). The disease is characterized by persistent neutrophilia in peripheral blood, bone marrow hypercellularity and hepatosplenomegaly. Neither a Philadelphia chromosome nor BCR/ABL1 fusion gene are found. Reactive neutrophilia and other myeloproliferative neoplasms (MPN) must be excluded.

Approximately 20% of patients show cytogenetic changes such as +8, +9, +21, del(20q), del(11q) and del(12p).

It has been recently shown that almost 100% of WHO defined chronic neutrophilic leukemia (CNL) patients have an acquired mutation in the CSF3R gene. These are predominantly exchanges from Threonine to Isoleucine at amino acid position 618 (T618I). However, CSF3R mutations have also been described in connection with hereditary chronic neutrophilia and severe congenital neutropenia (SCN). Inherited and acquired mutations e.g. in the ELANE gene are present in SCN, and are often accompanied by inherited leukemia progression. A mutation analysis of the ELANE gene can thus be used as demarcation of SCN to CNL.

Mutations in the ASXL1 gene can be detected in approximately 60% of patients. In one study, 33% of WHO defined CNL patients had an additional mutation in SETBP1. Both mutations are associated with unfavorable disease progression.