Activating CBL mutations are associated with a distinct MDS/MPN phenotype

Schwaab, Juliana, Ernst, Thomas, Erben, Philipp, Rinke, Jenny, Schnittger, Susanne, Ströbel, Philipp, Metzgeroth, Georgia, Mossner, Max, Haferlach, Torsten, Cross, Nicholas C. P., Hochhaus, Andreas, Hofmann, Wolf-Karsten and Reiter, Andreas (2012) Activating CBL mutations are associated with a distinct MDS/MPN phenotype. Annals of Hematology, 91 (11), 1713-1720. (doi:10.1007/s00277-012-1521-3).

Abstract

Activating point mutations in CBL have recently been identified in diverse subtypes of myeloid neoplasms. Because detailed clinical and hematological characteristics of CBL-mutated cases is lacking, we screened 156 BCR-ABL and JAK2 V617F negative patients with myeloproliferative neoplasms (MPN) and overlap syndromes between myelodysplastic syndrome (MDS) and MPN (MPS/MPN) for mutations in exons 8 and 9 of CBL by denaturing high-performance liquid chromatography and direct sequencing. CBL mutations were identified in 16/156 patients (10 %), of which five also carried mutations in EZH2 (n?=?3) and TET2 (n?=?2). Comprehensive clinical and hematological characteristics were available from 13/16 patients (81 %). In addition to splenomegaly (77 %), striking common hematological features were CML-like left-shifted leukocytosis (85 %) with monocytosis (85 %), anemia (100 %), and thrombocytopenia (62 %). Thrombocytosis was not observed in any patient. Relevant bone marrow features (n?=?12) included hypercellularity (92 %) with marked granulopoiesis (92 %), nonclustered microlobulated megakaryocytes (83 %), and marrow fibrosis (83 %). Nine deaths (progression to secondary acute myeloid leukemia/blast phase, n?=?7; cytopenia complications, n?=?2) were recorded. Three-year survival rate was 27 %, possibly indicating poor prognosis of CBL mutated MDS/MPN patients.

This record has no associated files available for download.

Contributors

Author: Nicholas C. P. Cross

Download statistics