XL SPI1 BA is designed as a break apart probe. The orange labeled probe hybridizes proximal to the breakpoint in the SPI1 gene region at 11p11.2, the green labeled probe hybridizes distal to the breakpoint.

Probe maps are created in accordance with the intended purpose of the product. Solid colored bars do not necessarily indicate that the probe fully covers the indicated genomic region. Therefore, caution is advised when interpreting results generated through off-label use. Probe map details based on UCSC Genome Browser GRCh37/hg19. Map components not to scale. Further information is available on request.

The SPI1 (SFFV provirus integration site-1) gene encodes the ETS-family transcription factor PU.1, which mediates gene expression during normal development of hematopoietic stem cells. SPI1 gene fusions were detected in 7 of 181 (3.9%) pediatric T-cell acute lymphoblastic leukemia (T-ALL) cases, analyzed and described by Seki et al. Genetic consequences of chromosomal rearrangements involving SPI1 are gene fusions containing 3' exons of SPI1 and 5' portions of TCF7, STMN1 and BCL11B. The cterminal DNA binding domain (ETS domain) of the PU.1 protein is present in all known fusions, irrespective of the fusion partner. Fusion-positive samples show strongly increased SPI1 expression levels, as the rearranged portion of SPI1 is placed under the control of heterologous promoters of the above-mentioned genes. As SPI1 is normally expressed as an early phase gene in T-cell development, expression of wildtype SPI1 or SPI1 fusion genes at later stages results in higher cell proliferation and differentiation/ maturation blockade during T-cell development. Fusion-positive cases show significantly shorter overall survival and are incurable when treated with standard chemotherapy.

SPI1 has recently been found to interact with the PML-RARα complex. Additionally, SPI1 itself is transcriptionally regulated by the PML-RARα fusion protein.

Clinical Applications

• Acute Lymphoblastic Leukemia (ALL)

XL SPI1 BA hybridized to lymphocytes. One normal interphase and one normal metaphase are shown.

• Martens and Stunnenberg (2010) FEBS Letters 584:2662-2669
• Seki et al (2017) Nat Genetics 49:1274- 1281
• Takei and Kobayashi (2019) Int J Hematol 109:28–34

• Utility and performance of bacterial artificial chromosomes-on-beads assays in chromosome analysis of clinical prenatal samples, products of conception and blood samples.
• A child with multiple congenital anomalies due to partial trisomy 7q22.1 → qter resulting from a maternally inherited balanced translocation: a case report and review of literature.
• Distinct roles of ATM and ATR in the regulation of ARP8 phosphorylation to prevent chromosome translocations.
• Heterogeneous MYCN amplification in neuroblastoma: a SIOP Europe Neuroblastoma Study.
• Immense random colocalization, revealed by automated high content image cytometry, seriously questions FISH as gold standard for detecting EML4-ALK fusion.
• Fluorescence in situ hybridisation assays designed for del(7q) detection uncover more complex rearrangements in myeloid leukaemia cell lines
• Detection of t(7;12)(q36;p13) in paediatric leukaemia using dual colour fluorescence in situ hybridisation.
• A rare case of t(11;22) in a mantle cell lymphoma like B-cell neoplasiaresulting in a fusion of IGL and CCND1: case report.
• Genomic DNA-chip hybridization in t(11;14)-positive mantle cell lymphomas shows a high frequency of aberrations and allows a refined characterization of consensus regions.