intheU937celllineresults inthefusion oftheAFJOgeneandCALM,encoding anewmemberofthe AP-3clathrin assembly protein family

ABSTRACT Thetranslocation t(10;11)(p13;q14) is arecur-ring chromosomal abnormality that has been observed in pa-tientswith acute lymphoblasticleukemia as well as acutemyeloidleukemia.Wehaverecentlyreportedthatthemonocyticcell lineU937has a t(10;11)(pl3;ql4)translocation.Using a combinationofpositionalcloningandcandidategeneapproach,weclonedthebreakpoint andwereable to show thatAF1Ois fused to anovelgene that we namedCALM(ClathrinAssemblyLymphoidMy-eloid leukemia gene) located at 11ql4. AFIO, a putative tran- scription factor, had recently been cloned as one ofthe fusionpartners of MLL. CALM has a very high homology in itsN-terminal third to the murine ap-3 gene which is one of theclathrin assembly proteins. The N-terminal region ofap-3 hasbeenshowntobindtoclathrinand to have a high-affinitybindingsite for phosphoinositols. Theidentification ofthe CALM/AFIOfusiongeneinthewidelyusedU937celllinewillcontribute toour understanding ofthe malignant phenotype ofthis line.The cloning of recurring