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Functional and genetic screening of acute myeloid leukemia associated with mediastinal germ cell tumor identifies MEK inhibitor as an active clinical agent.
- Source :
-
Journal of hematology & oncology [J Hematol Oncol] 2016 Mar 31; Vol. 9, pp. 31. Date of Electronic Publication: 2016 Mar 31. - Publication Year :
- 2016
-
Abstract
- Background: Hematologic malignancies arising in the setting of established germ cell tumors have been previously described and have a dismal prognosis. Identification of targetable mutations and pathway dysregulation through massively parallel sequencing and functional assays provides new approaches to disease management.<br />Case Presentation: Herein, we report the case of a 23-year-old male who was diagnosed with a mediastinal germ cell tumor and subsequent acute myeloid leukemia. A shared clonal origin was demonstrated through identification of identical NRAS and TP53 somatic mutations in both malignancies. The patient's leukemia was refractory to standard therapies with short interval relapse. Functional assays demonstrated the patient's blasts to be sensitive to the mitogen-activated protein kinase kinase (MEK) inhibitor trametinib, correlating with the activating NRAS mutation. The patient experienced a sustained partial remission while on trametinib therapy but ultimately suffered relapse of the germ cell tumor. The leukemic clone remained stable and sensitive to trametinib at that time.<br />Conclusions: This case highlights the potential power of combining genetic sequencing and in vitro functional assays with targeted therapies in the treatment of rare diseases.
- Subjects :
- Acute Disease
GTP Phosphohydrolases genetics
High-Throughput Nucleotide Sequencing
Humans
Leukemia, Myeloid complications
Leukemia, Myeloid genetics
MAP Kinase Kinase 1 antagonists & inhibitors
MAP Kinase Kinase 2 antagonists & inhibitors
Male
Mediastinal Neoplasms complications
Mediastinal Neoplasms genetics
Membrane Proteins genetics
Neoplasm Recurrence, Local
Neoplasms, Germ Cell and Embryonal complications
Neoplasms, Germ Cell and Embryonal genetics
Point Mutation
Protein Kinase Inhibitors therapeutic use
Treatment Outcome
Tumor Suppressor Protein p53 genetics
Young Adult
Leukemia, Myeloid drug therapy
Mediastinal Neoplasms drug therapy
Neoplasms, Germ Cell and Embryonal drug therapy
Pyridones therapeutic use
Pyrimidinones therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1756-8722
- Volume :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of hematology & oncology
- Publication Type :
- Academic Journal
- Accession number :
- 27036514
- Full Text :
- https://doi.org/10.1186/s13045-016-0258-1