There are a number of myeloid
disorders that have been related to mutations in G-CSFR (gene:CSF3R) including (Severe Congenital
Neutropenia (SCN), Chronic Neutrophilic Leukemia (CNL), Myelodysplastic
Syndrome (MDS), Acute Myeloid Leukemia (AML), atypical Chronic Myelogenous
Leukemia (aCML)) (1-3). The most prevalent of these
disorders is SCN. Many SCN patients treated with G-CSF (induction therapy), regain
a sufficient level of neutrophils to reduce infection related mortality.
However, a major concern is the leukemic progression of SCN into MDS or AML.
Specifically, SCN patients on G-CSF treatment can acquire somatic frame-shift
or nonsense mutations in the CSF3R, which have been shown to cause
truncations of the cytoplasmic region of the receptor (4-5). Surprisingly,
other CSF3R mutations (specially a point mutation close to the membrane
proximal region: proximal mutation T618I) are frequently observed de novo in
CNL which is characterized by hyper-responsiveness to
the growth factor leading to an excess of neutrophils