Myeloid/Lymphoid Neoplasm With FGFR1 Rearrangement Accompanying RUNX1 and NOTCH1 Gene Mutations

Xiaoxue Wang; Xinyue Huang; Hui Pang; Sheng Xiao; Hongcang Gu; Heyang Zhang; Baixun Wang; Lijun Zhang; Xiaojing Yan

doi:10.3389/fonc.2019.01304

Myeloid/Lymphoid Neoplasm With FGFR1 Rearrangement Accompanying RUNX1 and NOTCH1 Gene Mutations

Front Oncol. 2019 Nov 22:9:1304. doi: 10.3389/fonc.2019.01304. eCollection 2019.

Authors

Xiaoxue Wang^{1

2}, Xinyue Huang¹, Hui Pang², Sheng Xiao³, Hongcang Gu^{2

4}, Heyang Zhang¹, Baixun Wang¹, Lijun Zhang¹, Xiaojing Yan¹

Affiliations

¹ Department of Hematology, The First Hospital of China Medical University, Shenyang, Liaoning, China.
² Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States.
³ Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
⁴ Broad Institute of MIT and Harvard, Cambridge, MA, United States.

Abstract

Background: Myeloid/Lymphoid Neoplasm with FGFR1 Rearrangement is a rare kind of hematological malignant disease. Case presentation: A 37-year-old male patient experienced three distinct disease stages from myeloproliferative neoplasm (MPN), T-cell lymphoblastic lymphoma (T-LBL) to a much more complexed phage of a mixed phenotype acute leukemia (MPAL). Both genetic and genomic alternations were detected including chromosomal abnormality and genic mutations. Result: Karyotyping and fluorescence in situ hybridization (FISH) analysis of either bone marrow or lymph node sample confirmed the presence of the FGFR1 rearrangement. Amplifications of RUNX1, ERG, and U2AF1 genes were identified by next generation sequencing. Furthermore, a frame-shift variant of F330fs^*>149 in the RUNX1 gene and a missense mutation of R2263Q in NOTCH1 were also detected. Conclusion: The FGFR1 rearrangement functions as a trigging oncogenic event. Then other genetic events such as RUNX1 and/or NOTCH1 alternations further lead to progression of disease with trilineage blasts assignment.

Keywords: FGFR1; MPAL; MPN; Notch; Runx1.

Publication types

Case Reports