An abnormal clone with monosomy 7 and trisomy 21 in the bone marrow of a child with congenital agranulocytosis (Kostmann disease) treated with granulocyte colony-stimulating factor. Evolution towards myelodysplastic syndrome and acute basophilic leukemia.
Cytogenetic analysis of bone marrow cells revealed an abnormal clone with monosomy 7 and trisomy 21 in a 12-year-old child with Kostmann disease (KD). The patient presented with anemia, thrombocytopenia, and splenomegaly after 5 years of treatment with granulocyte colony-stimulating factor (G-CSF). The bone marrow morphology was consistent with the diagnosis of myelodysplastic syndrome (MDS). Administration of G-CSF was discontinued at this point. Bone marrow studies 2 and 5 months later showed persistence of both myelodysplasia and the abnormal clone with monosomy 7 and trisomy 21. Monosomy 7 was also confirmed by fluorescence in situ hybridization (FISH). After 2 months of follow-up, the patient presented with acute basophilic leukemia, a very rare variant of acute myeloid leukemia (AML), expressing the same bone marrow chromosome abnormalities as observed earlier. This is a rare case of KD with prolonged survival and a cytogenetically abnormal clone evolving to MDS and acute basophilic leukemia. The significance of monosomy 7 and trisomy 21 in KD treated with G-CSF is discussed.
Department of Human Genetics, University of Pittsburgh, Pennsylvania, USA.
S
S
Shekhter-Levin
L
L
Penchansky
M R
MR
Wollman
M E
ME
Sherer
N
N
Wald
S M
SM
Gollin
D000380:Agranulocytosis / Q000151:congenital* / Q000628:therapy; D002648:Child; D002891:Chromosomes, Human, Pair 21; D002897:Chromosomes, Human, Pair 7; D004314:Down Syndrome / Q000235:genetics*; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007621:Karyotyping; D015471:Leukemia, Basophilic, Acute / Q000235:genetics*; D008297:Male; D009006:Monosomy; D009190:Myelodysplastic Syndromes / Q000235:genetics*
D016179:Granulocyte Colony-Stimulating Factor