Next-Generation Sequencing Technology Reveals a Characteristic Pattern of Molecular Mutations in 72.8% of Chronic Myelomonocytic Leukemia by Detecting Frequent Alterations in TET2, CBL, RAS, and RUNX1

作者：Kohlmann Alexander^*; Grossmann Vera; Klein Hans Ulrich; Schindela Sonja; Weiss Tamara; Kazak Beray; Dicker Frank; Schnittger Susanne; Dugas Martin; Kern Wolfgang; Haferlach Claudia; Haferlach Torsten

来源：Journal of Clinical Oncology, 2010, 28(24): 3858-3865.

DOI：10.1200/JCO.2009.27.1361

Purpose
Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic malignancy that is characterized by features of both a myeloproliferative neoplasm and a myelodysplastic syndrome. Thus far, data on a comprehensive cytogenetic or molecular genetic characterization are limited.
Patients and Methods
Here, we analyzed 81 thoroughly characterized patients with CMML (CMML type 1, n = 45; CMML type 2, n =36) by applying next-generation sequencing (NGS) technology to investigate CBL, JAK2, MPL, NRAS, and KRAS at known mutational hotspot regions. In addition, complete coding regions were analyzed for RUNX1 (= isoform) and TET2 aberrations.
Results
Cytogenetic aberrations were found in 18.2% of patients (14 of 77 patients). In contrast, at least one molecular mutation was observed in 72.8% of patients (59 of 81 patients). A mean of 1.6 mutations per patient was observed by this unprecedented screening. In total, 105 variances were detected by this comprehensive molecular screening. After excluding known polymorphisms or silent mutations, 82 distinct mutations remained (CBL, n = 15; JAK2V617F, n =8; MPL, n = 0; NRAS, n = 10; KRAS, n = 12; RUNX1, n =7; and TET2, n = 41). With respect to clinical data, a better outcome was seen for patients carrying TET2 mutations (P =.013).
Conclusion
The number of molecular markers used to categorize myeloid neoplasms is constantly increasing. Here, NGS screening has been demonstrated to support a comprehensive characterization of the molecular background in CMML. A

• 出版日期2010-8-20