t(3;5)(p21;q32) RBM6/CSF1R
2010-12-01 Jean-Loup Huret Affiliation1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Clinics and Pathology
Disease
MKPL-1 cell line, established from a 66-year-old male patient with an acute megakaryoblastic leukemia (M7-AML) and a karyotype apparently with -21,+3mar (Takeuchi et al., 1992), re-analysed for tyrosine kinase dysregulation (Gu et al., 2007).
Epidemiology
Only one case to date.
Genes Involved and Proteins
Gene name
RBM6 (RNA binding motif protein 6)
Location
3p21.31
Protein description
From N-term to C-term, contains a BTB/POZ domain (mediates homomeric dimerization) and decamer repeat domains, responsible for multimerization/self-association of the protein, RRM1 and RRM2 (RNA recognition motif) domains, an octamer repeat, a C2H2 zinc finger, a nuclear localisation signal, and a G-patch (made of highly conserved glycines; may have RNA binding functions). RNA-binding protein. Binds poly(G). Splicing factor (Heath et al., 2010).
Gene name
CSF1R (colony stimulating factor 1 receptor, formerly McDonough feline sarcoma viral (v-fms) oncogene homolog)
Location
5q32
Protein description
Contains Ig-like domains (extracellular), a transmembrane domain, and a split tyrosine kinase domain (intracellular), from N-term to C-term. Transmembrane glycoprotein, receptor for the ligand colony stimulating factor-1 (CSF1). Upon binding of CSF1, CSF1R tyrosine phosphorylation is induced leading to RAS/RAF/MAPK, PI3K/AKT/mTOR and JAK/STAT (specifically STAT1, STAT3, and STAT5) pathways activation. CSF1R activation by CSF1 results in increased growth, proliferation and differentiation (Fischer et al., 2008).
Result of the Chromosomal Anomaly
Description
Fusion of RBM6 exon 2 to CSF1R exon 12; the reciprocal CSF1R-RBM6 was not detected.The RBM6-CSF1R fusion protein consists of the amino terminal 36 amino acids of RBM6, fused to the carboxy terminal 399 amino acids of CSF1R, including a polymerisation domain of RBM6, and the tyrosine kinase domain of CSF1R.
Oncogenesis
Constitutive tyrosine kinase activation.
Highly cited references
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 17360941 | 2007 | A novel fusion of RBM6 to CSF1R in acute megakaryoblastic leukemia. | 43 |
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 17360941 | 2007 | A novel fusion of RBM6 to CSF1R in acute megakaryoblastic leukemia. | Gu TL et al |
| 21086038 | 2010 | Subnuclear targeting of the RNA-binding motif protein RBM6 to splicing speckles and nascent transcripts. | Heath E et al |
| 1602796 | 1992 | Acute megakaryoblastic leukemia: establishment of a new cell line (MKPL-1) in vitro and in vivo. | Takeuchi S et al |
Summary
Fusion gene
RBM6/CSF1R RBM6 (3p21.31) CSF1R (5q32) M t(3;5)(p21;q33)|RBM6/CSF1R RBM6 (3p21.31) CSF1R (5q32) TIC
Citation
Jean-Loup Huret
t(3;5)(p21;q32) RBM6/CSF1R
Atlas Genet Cytogenet Oncol Haematol. 2010-12-01
Online version: http://atlasgeneticsoncology.org/haematological/2139/t(3;5)(p21;q32)-rbm6-csf1r
