Molecular Profiling of Myeloid Progenitor Cells in Multi-mutated Advanced Systemic Mastocytosis Identifies KIT D816V As a Distinct and Late Event

Overview

Journal Leukemia

Specialties Hematology
Oncology

Date 2015 Jan 9

PMID 25567135

Citations 66

Authors

M Jawhar

J Schwaab

S Schnittger

K Sotlar

H-P Horny

G Metzgeroth

N Muller

S Schneider

N Naumann

C Walz

T Haferlach

P Valent

W-K Hofmann

N C P Cross

A Fabarius

A Reiter

Affiliations

Soon will be listed here.

Abstract

To explore the molecular profile and its prognostic implication in systemic mastocytosis (SM), we analyzed the mutation status of granulocyte-macrophage colony-forming progenitor cells (CFU-GM) in patients with KIT D816V(+) indolent SM (ISM, n=4), smoldering SM (SSM, n=2), aggressive SM (ASM, n=1), SM with associated clonal hematologic non-mast cell lineage disorder (SM-AHNMD, n=5) and ASM-AHNMD (n=7). All patients with (A)SM-AHNMD (n=12) carried 1-4 (median 3) additional mutations in 11 genes tested, most frequently TET2, SRSF2, ASXL1, CBL and EZH2. In multi-mutated (A)SM-AHNMD, KIT D816V(+) single-cell-derived CFU-GM colonies were identified in 8/12 patients (median 60%, range 0-95). Additional mutations were identified in CFU-GM colonies in all patients, and logical hierarchy analysis indicated that mutations in TET2, SRSF2 and ASXL1 preceded KIT D816V. In ISM/SSM, no additional mutations were detected and CFU-GM colonies were exclusively KIT D816V(-). These data indicate that (a) (A)SM-AHNMD is a multi-mutated neoplasm, (b) mutations in TET2, SRSF2 or ASXL1 precede KIT D816V in ASM-AHNMD,

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