A Gene for a Myos in Peptide Is Disrupted by the inv ( l 6 ) ( p 13 q 22 ) in Acute Nonlymphocytic Leukemia M 4 Eo

ECURRENT chromosomal aberrations seen in leukeR mic cells have led to the cloning of numerous breakpoints and the subsequent identification of genes involved in leukemogenesis.’ The most frequent chromosome I6 aberration associated with acute nonlymphocytic leukemia (ANLL) subtype M4Eo (according to French-American-British [FAB] classification*) is the inv( 16)(pl3q22), first reported in 1983.3 In a small minority of the patients with ANLL, deletions of the long arm and other aberrations of chromosome 16 have been There is an indication that a clinicopathologic association exists between the development of granulocytic sarcomas in the small intestine and ANLL M4Eo. A comparable correlation has been described for ANLL M4Eo and the involvement of the central nervous system.3,9s’0 Unravelling the molecular structure around the inv( 16) breakpoints and the possible identification of adjacent genes should give insight into the mechanisms ofleukemogenesis in chromosome 16-associated ANLL M4Eo. In earlier studies using fluorescence in situ hybridization (FISH) with cosmids, we mapped the inv( 16) and t( 16;16) breakpoints to a specific interval on chromosome 16, band 1 6 ~ 1 3 . ” , ’ ~ The interval was closed by screening two YAC l ibrar ie~’~?’~ with polymerase chain reaction (PCR), which yielded 5 YACs. FISH of the YACs to metaphase spreads from I7 patients showed that all of the YACs spanned the inv( 16) and t( 16; 16) breakpoints. The subcloning of the YACs led to the identification of a 14-kb genomic EcoRI fragment that spans the breakpoints in 5 inv( 16) patients tested. Southern blot analysis with fragments derived from the 14-kb EcoRI fragment hybridized