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Here, we show that an elevated level of ABL1 kinase overactivates the HR pathway and causes genomic instability in multiple myeloma (MM) cells. Inhibiting ABL1 with either short hairpin RNA or a pharmacological inhibitor (nilotinib) inhibits HR activity, reduces genomic instability, and slows MM cell growth. Moreover, inhibiting ABL1 reduces the HR activity and genomic instability caused by melphalan, a chemotherapeutic agent used in MM treatment, and increases melphalan\u2019s efficacy and cytotoxicity in\u00a0vivo in a subcutaneous tumor model. In these tumors, nilotinib inhibits endogenous as well as melphalan-induced HR activity. These data demonstrate that inhibiting ABL1 using the clinically approved drug nilotinib reduces MM cell growth, reduces genomic instability in live cell fraction, increases the cytotoxicity of melphalan (and similar chemotherapeutic agents), and can potentially prevent or delay progression in patients with MM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2023021225","type":"journal-article","created":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T15:10:57Z","timestamp":1700665857000},"page":"996-1005","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":5,"title":["ABL1 kinase plays an important role in spontaneous and chemotherapy-induced genomic instability in multiple myeloma"],"prefix":"10.1182","volume":"143","author":[{"given":"Subodh","family":"Kumar","sequence":"first","affiliation":[{"name":"1The Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, 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