title: Systemic mastocytosis with associated clonal hematological non-mast-cell lineage disease: analysis of clinicopathologic features and activating c-kit mutations.
abstract: The majority of patients with systemic mastocytosis with associated clonal, hematological non-mast cell lineage disease (SM-AHNMD) have a myeloid stem cell malignancy including myelodysplastic syndromes (MDS), myelodysplastic/myeloproliferative disorders, acute myeloid leukemia (AML), or chronic myeloproliferative disease. The clinicopathologic features of SM-AHNMD have not been fully characterized. We describe seven cases of this entity: 3 with MDS, 3 with AML, and 1 with chronic myelomonocytic leukemia. In the majority of cases, SM was diagnosed concurrently with the myeloid malignancy and aberrant mast cell morphology was observed. The commonly described c-kit enzymatic site mutation Asp816Val was detected only in 2 cases, while 3 patients carried the Asp816His mutation. Among the 3 cases with AML, 2 patients carried the translocation t(8;21). On the basis of our results and other reported cases, there appears to be a specific association between SM and AML with t(8;21). Concurrent occurrence of SM may define a subset of patients with de novo AML and other myeloid malignancies who have an adverse prognosis. As clinically effective tyrosine kinase inhibitors that inhibit enzymatic-type c-kit mutations are being developed, detection of mast cell proliferation associated with myeloid malignancy may have important therapeutic implications.
authors.affiliation: Division of Hematology, University of Southern California Keck School of Medicine, Los Angeles, CA, USA. vinodpullarkat@pol.net
authors.forename: Vinod A
authors.initials: VA
authors.lastname: Pullarkat
authors.forename: Carlos
authors.initials: C
authors.lastname: Bueso-Ramos
authors.forename: Raymond
authors.initials: R
authors.lastname: Lai
authors.forename: Steven
authors.initials: S
authors.lastname: Kroft
authors.forename: Carla S
authors.initials: CS
authors.lastname: Wilson
authors.forename: Sheeja T
authors.initials: ST
authors.lastname: Pullarkat
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Bu
authors.forename: Maung
authors.initials: M
authors.lastname: Thein
authors.forename: M
authors.initials: M
authors.lastname: Lee
authors.forename: Russell K
authors.initials: RK
authors.lastname: Brynes
mesh_terms: D000328:Adult; D000368:Aged; D000754:Anemia, Refractory, with Excess of Blasts / Q000235:genetics / Q000473:pathology; D002880:Chromosomes, Human, Pair 11; D002881:Chromosomes, Human, Pair 12; D002891:Chromosomes, Human, Pair 21; D002895:Chromosomes, Human, Pair 5; D002898:Chromosomes, Human, Pair 8; D005260:Female; D017353:Gene Deletion; D006402:Hematologic Diseases / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000473:pathology; D015477:Leukemia, Myelomonocytic, Chronic / Q000235:genetics / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000473:pathology*; D034721:Mastocytosis, Systemic / Q000235:genetics* / Q000473:pathology*; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000473:pathology; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D019009:Proto-Oncogene Proteins c-kit