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Patient with rare disorder responds to cancer drug

A rare disorder caused by an excess of two types of immune cellsthe mast cell found in various tissues and its blood-based twin, the basophilhas successfully been treated with a cancer drug, report scientists from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). The study, now available online at the Web site of the journal Haematologica, was a collaborative effort led by Dean Metcalfe, M.D., chief of the NIAID Laboratory of Allergic Diseases and Jan Cools, Ph.D., a staff scientist, at the Katholieke Universiteit Leuven within the Vlaams Institute for Biotechnology and the Department of Molecular and Developmental Genetics, in Leuven, Belgium.

A few years ago, the 61-year-old patient was referred to the NIH Clinical Center because he was quite ill with symptoms of systemic mastocytosis, a disease caused by excessive numbers of mast cells, and chronic basophilic leukemia, a rare type of bone marrow cancer characterized by an overabundance of basophils.

Systemic mastocytosis often results from a mutation in the gene that codes for the KIT receptor found on the surface of mast cells, a discovery first made by Dr. Metcalfe and his team in 1995. In this patient, however, the KIT receptor mutation was ruled out. In further studies, NIAID researchers and their collaborators found a chromosomal abnormality that led to the discovery of a fusion protein in the cell, created by two genes joining together. They also found that the fusion protein was the basis of the disorder and figured that the patient should respond to imatinib, a drug already approved to treat different types of cancers and systemic mastocytosis. After the patient was treated with the cancer drug imatinib, his clinical symptoms improved quickly and dramatically, and he remains in clinical remission three years after treatment was started.

This is a rare report of the simultaneous occurrence of these two conditions in one patient, and the first describing a response to therapy. Diagnosing a patient who has such an atypical disorder can be difficult, says Dr. Metcalfe. Recently, another patient with similar clinical findings was referred to their clinic. Based on their experience with the first patient, the researchers started treatment with imatinib and, according to Dr. Metcalfe, this patient also is responding well.

Identifying this newly recognized chromosomal abnormality and the fusion protein in patients who present with clinical findings of systemic mastocytosis and chronic basophilic leukemia may enable doctors to successfully treat these individuals with imatinib, according to Dr. Metcalfe.


Contact: Sitara Maruf
NIH/National Institute of Allergy and Infectious Diseases

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