title: Systemic mastocytosis with associated clonal hematological non-mast cell lineage disease: clinical significance and comparison of chomosomal abnormalities in SM and AHNMD components.
abstract: Some patients with systemic mastocytosis have concurrent hematological neoplasms, designated in the World Health Organization (WHO) classification as systemic mastocytosis with associated clonal hematological non-mast cell lineage disease (SM-AHNMD). In this study, we analyzed 29 patients with SM-AHNMD and compared them to 40 patients with pure SM. The AHNMDs were classified as chronic myelomonocytic leukemia (CMML) (n = 10), myelodysplastic syndrome (MDS) (n = 7), myeloproliferative neoplasms (n = 4), B-cell lymphoma/leukemia/plasma cell neoplasms (n = 7), and acute myeloid leukemia (n = 1). Patients with SM-AHNMD were older, more frequently had constitutional symptoms and hematological abnormalities, less often had skin lesions, and had an inferior overall survival compared with pure SM patients (48 months vs. not-reached, P < 0.001). Karyotypic abnormalities were detected in 9/28 (32%) patients with SM-AHNMD but not in pure SM patients (P < 0.001). Combined imaging/ fluorescence-in-situ hybridization performed in four SM-AHNMD cases revealed shared abnormal signals in mast cells and myeloid cells in two patients with SM-CMML and one patient with SM-MDS, but not in the mast cells of a case SM-associated with chronic lymphocytic leukemia with ATM-deletion. Quantitative mutation analysis showed higher levels of mutant KIT D816V in SM-CMML and SM-MDS than in pure SM (P < 0.001). Our data indicate that the SM-AHNMD category in the WHO classification is heterogeneous, including clonally related and unrelated forms of AHNMD. The presentation, treatment, and outcome of patients with SM-AHNMD is often dictated by the type of AHNMD.
authors: Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. swang5@mdanderson.org
authors: Sa A
authors: SA
authors: Wang
authors: Lloyd
authors: L
authors: Hutchinson
authors: Guilin
authors: G
authors: Tang
authors: Su S
authors: SS
authors: Chen
authors: Patricia M
authors: PM
authors: Miron
authors: Yang O
authors: YO
authors: Huh
authors: Dan M
authors: DM
authors: Jones
authors: Carlos
authors: C
authors: Bueso-Ramos
authors: Srdan
authors: S
authors: Verstovsek
authors: L Jeffrey
authors: LJ
authors: Medeiros
authors: Roberto N
authors: RN
authors: Miranda
mesh_terms: D059786:Abnormal Karyotype; D000328:Adult; D000367:Age Factors; D000368:Aged; D019070:Cell Lineage; D002999:Clone Cells; D004252:DNA Mutational Analysis; D005260:Female; D019337:Hematologic Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D015477:Leukemia, Myelomonocytic, Chronic / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology*; D034721:Mastocytosis, Systemic / Q000145:classification / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D015996:Survival Rate
chemical_list: D019009:Proto-Oncogene Proteins c-kit