Mol Pathol  2000 Aug;53(4):188-93 

Detection of c-kit mutation Asp 816 to Val in microdissected bone marrow
infiltrates in a case of systemic mastocytosis associated with chronic
myelomonocytic leukaemia.

Sotlar K, Marafioti T, Griesser H, Theil J, Aepinus C, Jaussi R, Stein H, Valent
P, Horny HP.

Institute of Pathology, University Hospital Tubingen, Germany.

BACKGROUND/AIMS: The occurrence of myeloid leukaemia in patients with systemic
mastocytosis is a well recognised phenomenon. However, the pathophysiological
basis of such a coevolution has not been clarified. Recent data have shown that
the c-kit mutation Asp 816 to Val is detectable in neoplastic mast cells in most
patients with systemic mastocytosis, including those who have associated
haematological disorders. The aim of this study was to study clonal disease
evolution by analysing bone marrow cells from a patient with systemic
mastocytosis and associated chronic myelomonocytic leukaemia (CMML) for the
presence of this mutation. METHODS: The DNA of microdissected bone marrow cells
from a patient with systemic mastocytosis and associated CMML was analysed for
the presence of the c-kit mutation Asp 816 to Val by means of HinfI digestion
and direct sequencing of semi-nested polymerase chain reaction (PCR) products.
RESULTS: The two neoplasms could easily be identified and discriminated in
paraffin wax embedded bone marrow sections by tryptase and chloroacetate
esterase staining. A total number of 10 tryptase positive systemic mastocytosis
infiltrates and 10 tryptase negative CMML infiltrates were removed by
microdissection. As assessed by HinfI digestion and direct sequencing of
semi-nested PCR products, the c-kit mutation Asp 816 to Val was detected in five
of seven systemic mastocytosis infiltrates and four of six CMML infiltrates. By
contrast, no c-kit mutation Asp 816 to Val was found in bone marrow infiltrates
in patients with CMML without associated systemic mastocytosis (n = 20).
CONCLUSION: These data support a monoclonal evolution of systemic mastocytosis
and concurrent CMML in the patient studied.

PMID: 11040941 [PubMed - indexed for MEDLINE]