Details

Autor(en) / Beteiligte

• Kanayama, Takuyo
• Imamura, Toshihiko
• Mayumi, Azusa
• Soma, Emi
• Sakamoto, Kenichi
• Hayakawa, Fumihiko
• Tanizawa, Akihiko
• Kiyokawa, Nobutaka
• Hosoi, Hajime

Titel

Functional analysis of a novel fusion protein PAX5-KIDINS220 identified in a pediatric Ph-like ALL patient

Ist Teil von

• International journal of hematology, 2020-11, Vol.112 (5), p.714-719

Ort / Verlag

Singapore: Springer Singapore

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• PAX5-KIDINS220 ( PAX5-K220 ) is a novel chimeric fusion gene identified in a pediatric Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL) patient, but the function of the encoded fusion protein has not yet been analyzed. Here, we report the functional analysis of PAX5-K220 in vitro. We successfully generated PAX5-K220 expressing cells and demonstrate that PAX5-K220 is a nuclear protein. Luciferase reporter assay reveals that PAX5-K220 inhibits wild-type PAX5 transcriptional activity in a dominant-negative fashion like other PAX5-related fusion proteins, and may contribute to lymphocyte differentiation block. However, although identified in Ph-like ALL, PAX5-K220 does not induce IL-3-independent proliferation when transduced in the IL-3-dependent Ba/F3 murine leukemia cells, but rather attenuates growth. These results reveal that PAX5-K220 certainly shares the character with other PAX5-related fusion proteins rather than other fusion proteins with tyrosine kinase activity identified in Ph-like ALL, and did not contribute to proliferation activity. Precise functional analysis of each differently partnered PAX5 fusion protein is warranted in the future for better understanding of PAX5-related translocations and their effects.