PHILADELPHIA-NEGATIVE CHRONIC MYELOGENOUS LEUKEMIA IN A PATIENT WITH A UNIQUE COMPLEX TRANSLOCATION - 46,XY,T(9-12-15)(Q34-Q12-Q21)

Chronic myelogenous leukemia (CML) is associated with an acquired kary otypic abnormality, the Philadelphia (Ph) chromosome, in 95% of cases. The Ph chromosome is the product of a balanced translocation that res ults in a hybrid gene that is considered essential for the pathogenesi s of this disease. We have found a complex translocation involving chr omosomes 9, 12, and 15 in a 42-year-old Haitian male with the clinical findings of CML. Complex translocations have been shown to result in the masking of the Ph chromosome. We used a mixture of two BCR-specifi c DNA probes for Southern blot analysis in order to test this hypothes is in our patient. High-molecular weight DNA was digested with the res triction enzymes BglII, BamHI and HindIII. The BglII digestion reveale d the presence of two abnormal fragments of 3.9 and 3.0 kb and the Bam HI digestion an abnormal 15-kb fragment. These data suggest there is a breakpoint in region 2 of M-bcr. The identification of this breakpoin t confirms our hypothesis that a rearrangement involving 22q11 has occ urred in the leukemic cells of our patient. A secondary translocation involving chromosomes 12 and 15 has hidden the effects of this translo cation. Combined cytogenetic and molecular analysis establishes the ka ryotype of our patient as 46,XY,t(9;12;15;22)(q34;q12;q21;q11). (C) 19 98 Elsevier Science Ltd. All rights reserved.