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.We successfully generated PAX5-K220 expressing cells and demonstrate that PAX5-K220 is a nuclear protein. In addition, PAX5-K220 activates JAK2-STAT5 pathway through the repression of Socs5, a known negative regulator of JAK-STAT pathway. 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. 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. 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. Overall design: To reveal which pathways were affected by PAX5-KISINS220 (P-K220), Ba/F3 cells transduced with P-K220 fusion protein by the Retro-X Tet-on Advanced Inducible System (Clontech) were cultured with or without 500 ng/mL doxycycline (in other words, with or without expression of P-K220), and 24 hours later, total RNA were extracted from Ba/F3 with or without expression of P-K220.