Mutational spectrum of myeloid malignancies with inv(3)/t(3;3) reveals a predominant involvement of RAS/RTK signaling pathways

SM Groschel, Mathijs Sanders, Remco Hoogenboezem, Annelieke Zeilemaker, Marije Havermans, Claudia Erpelinck - Verschueren, Eric Bindels, Berna Beverloo, H Dohner, Bob Löwenberg, K Dohner, Ruud Delwel, Peter Valk

Research output: Contribution to journalArticleAcademicpeer-review

72 Citations (Scopus)


Myeloid malignancies bearing chromosomal inv(3)/t(3; 3) abnormalities are among the most therapy-resistant leukemias. Deregulated expression of EVI1 is the molecular hallmark of this disease; however, the genome-wide spectrum of cooperating mutations in this disease subset has not been systematically elucidated. Here, we show that 98% of inv(3)/t(3; 3) myeloid malignancies harbor mutations in genes activating RAS/receptor tyrosine kinase (RTK) signaling pathways. In addition, hemizygous mutations in GATA2, as well as heterozygous alterations in RUNX1, SF3B1, and genes encoding epigenetic modifiers, frequently co-occur with the inv(3)/t(3; 3) aberration. Notably, neither mutational patterns nor gene expression profiles differ across inv(3)/t(3; 3) acute myeloid leukemia, chronicmyeloid leukemia, andmyelodysplastic syndromecases, suggestingrecognitionof inv(3)/t(3; 3) myeloid malignancies as a single disease entity irrespective of blast count. The high incidence of activating RAS/RTK signalingmutations may provide a target for a rational treatment strategy in this high-risk patient group.
Original languageUndefined/Unknown
Pages (from-to)133-139
Number of pages7
Issue number1
Publication statusPublished - 2015

Research programs

  • EMC MGC-02-96-01
  • EMC MM-02-41-03

Cite this