MOLECULAR CYTOGENETICS OF CHRONIC MYELOID-LEUKEMIA WITH ATYPICAL T(6-9)(P23-Q35) TRANSLOCATION

We report the molecular cytogenetic analysis of a case of Philadelphia (Ph)-negative, BCR-positive chronic myeloid leukemia (CML) which appe ared by conventional cytogenetics to have a t(6;9)(p23;q34) as the sol e cytogenetic abnormality. Neither conventional nor pulse-field Southe rn blots detected any rearrangement of the DEK or CAN genes which are often fused in acute myeloid leukemia (AML) with t(6;9)(p23;q34). Howe ver, rearrangements of both BCR and ABL genes were detected. The break point in BCR was located in the major translocation cluster region bet ween exons bl and b3. ABL rearrangements were detected with an ABL exo n 1B probe and with a probe located 5' of the entire ABL gene. Comigra tion between the rearranged fragments obtained with M-bcr-5' and ABL e xon 1B probes was observed, implying that the entire ABL gene was fuse d to the 5' part of the BCR gene. Fluorescence in situ hybridization ( FISH) analyses using BCR and ABL probes showed that in 20% of metaphas es BCR and ABL signals were present on one chromosome 6 at 6p23, whils t in 80% of metaphases BCR and ABL signals were identified on both cop ies of chromosome 6. Furthermore, FISH analysis with a whole-chromosom e 22 paint demonstrated that chromosome 22 material was present on bot h copies of chromosome 6. These data indicate a complex Philadelphia t ranslocation involving chromosome band 6p23 and duplication of the who le aberrant chromosome. The nature of the gene locus on 6p23, involved in this rearrangement, remains unknown. A similar translocation has b een previously reported in a case of CML, which also lacked DEK and CA N gene rearrangements implying that abnormalities of 6p23 involving ge nes other than DEK may be a recurrent abnormality in CML.