Mast cell leukemia: identification of a new c-Kit mutation, dup(501-502), and response to masitinib, a c-Kit tyrosine kinase inhibitor.

Abstract

OBJECTIVE:

Most patients with systemic mastocytosis bear mutations in the tyrosine kinase receptor gene c-Kit. Limited treatment options exist for mast cell leukemia, a rare form of systemic mastocytosis associated with a dire prognosis. Our aim was to investigate c-Kit mutations associated with mast cell leukemia and find new treatment for this severe form of mastocytosis.

PATIENT AND METHODS:

We describe here a patient with mast cell leukemia characterized by 42% of circulating mast cells associated with a previously unidentified c-Kit mutation in adult mastocytosis: dup(501-502).

MAIN FINDINGS:

This patient was treated with masitinib, a novel c-Kit tyrosine kinase inhibitor, with a dramatic response observed following 3 months of treatment, including clinical improvement, disappearance of circulating mast cells, and decrease in both serum histamine and tryptase levels. In vitro and ex vivo research was performed on the patient's cells and revealed constitutive c-Kit phosphorylation in mast cell leukemia.

CONCLUSIONS:

This case highlights the importance of sequencing all c-Kit exons when the classical D816V c-Kit mutation is not found, even in adults with SM. It also indicates that masitinib may be safe and effective for the treatment for some mast cell leukemia.

• Authors: Sophie Georgin-Lavialle, Ludovic Lhermitte, Felipe Suarez, Ying Yang, Sébastien Letard, Katia Hanssens, Frédéric Feger, Amédée Renand, Chantal Brouze, Danielle Canioni, Vahid Asnafi, Marie-Olivia Chandesris, Achille Aouba, Paul Gineste, Elizabeth Macintyre, Colin D Mansfield, Alain Moussy, Yves Lepelletier, Patrice Dubreuil, Olivier Hermine
• Journal: European journal of haematology (Eur J Haematol) Vol. 89 Issue 1 Pg. 47-52 (Jul 2012) ISSN: 1600-0609 [Electronic] England
• PMID: 22324351 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 John Wiley & Sons A/S.

Chemical References

• Antineoplastic Agents
• Benzamides
• Piperidines
• Protein Kinase Inhibitors
• Pyridines
• Thiazoles
• Proto-Oncogene Proteins c-kit
• Tryptases
• masitinib

Topics

• Aged
• Animals
• Antineoplastic Agents (therapeutic use)
• Base Sequence
• Benzamides
• COS Cells
• Chlorocebus aethiops
• Female
• Humans
• Immunophenotyping
• Leukemia, Mast-Cell (drug therapy, genetics)
• Mast Cells (metabolism, pathology)
• Mutation
• Neoplastic Cells, Circulating (metabolism, pathology)
• Piperidines
• Protein Kinase Inhibitors (therapeutic use)
• Proto-Oncogene Proteins c-kit (genetics)
• Pyridines
• Thiazoles (therapeutic use)
• Tryptases (blood)