High frequency of concomitant mastocytosis in patients with acute myeloid leukemia exhibiting the transforming KIT mutation D816V.

The KIT mutation D816V is associated with autonomous growth of mast cells (MC) and is detectable in most patients with systemic mastocytosis (SM), including cases with associated hematologic non-MC-lineage disease (AHNMD). Recently, KIT D816V was reported to be expressed in patients with acute myeloid leukemia (AML). However, it was not clarified whether these patients have co-existing occult SM. We investigated neoplastic cells in 101 patients with AML for expression of KIT D816V. In 7/101 patients (6.9%), KIT D816V was detectable. After a thorough histologic, molecular, and biochemical analysis, all 7 cases were found to have an associated SM, leading to the final diagnosis SM-AML. Microdissected tryptase+ MC displayed KIT D816V in all patients tested, whereas CD34+ blasts exhibited KIT D816V in only 2/4 patients. In one AML patient, SM without KIT D816V was detected. In all other patients, no associated SM was found, and leukemic blasts were negative for KIT D816V. In summary, our data show that KIT D816V in AML is highly associated with co-existing SM (SM-AML). Moreover, our data show that AML blasts may lack this transforming target-mutant, which may be important when considering the use of KIT D816V-targeting drugs for treatment of patients with KIT D816V-positive AML.