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


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).


RESULTS
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.
Centre de Référence des Mastocytoses, Faculté de Médecine et AP-HP Necker-Enfants Malades, Paris, France.
Sophie
S
Georgin-Lavialle
Ludovic
L
Lhermitte
Felipe
F
Suarez
Ying
Y
Yang
Sébastien
S
Letard
Katia
K
Hanssens
Frédéric
F
Feger
Amédée
A
Renand
Chantal
C
Brouze
Danielle
D
Canioni
Vahid
V
Asnafi
Marie-Olivia
MO
Chandesris
Achille
A
Aouba
Paul
P
Gineste
Elizabeth
E
Macintyre
Colin D
CD
Mansfield
Alain
A
Moussy
Yves
Y
Lepelletier
Patrice
P
Dubreuil
Olivier
O
Hermine
D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001483:Base Sequence; D001549:Benzamides; D019556:COS Cells; D002522:Chlorocebus aethiops; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007946:Leukemia, Mast-Cell / Q000188:drug therapy* / Q000235:genetics*; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology; D010880:Piperidines; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D011725:Pyridines; D013844:Thiazoles / Q000627:therapeutic use; D053802:Tryptases / Q000097:blood
D000970:Antineoplastic Agents; D001549:Benzamides; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D013844:Thiazoles; D019009:Proto-Oncogene Proteins c-kit; D053802:Tryptases; C526575:masitinib