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DC van der Plas, AB Hermans, D Soekarman, EM Smit, A de Klein, N Smadja, G Alimena, R Goudsmit, G Grosveld and A Hagemeijer
Department of Cell Biology & Genetics, Erasmus University, Rotterdam,
The Netherlands.
We studied the clinical, hematologic, cytogenetic and molecular biologic
features in four patients with Philadelphia (Ph) negative chronic myeloid
leukemia (CML). In all four cases the clinical and hematologic
characteristics were indistinguishable from Ph positive CML. Cytogenetic
analysis showed a normal karyotype in two patients and chromosomal
translocations apparently not affecting chromosome 22 in the other two
cases. Southern blot analysis using probes of the bcr region, demonstrated
a bcr break-point in all four patients. In situ hybridization with bcr,
c-abl, and c-sis probes showed unusual hybridization sites for 5'-bcr and
c-abl indicating complex chromosomal rearrangements affecting three
different chromosomes in the four patients investigated. Using polymerase
chain reaction (PCR) followed by hybridization to oligonucleotide probes
specific for the bcr-abl fusion region, the expression of a chimeric
bcr-abl mRNA was detected. In these patients we demonstrated that (a) CML
with a breakpoint in the bcr region without cytogenetically detectable Ph
chromosome is characterized by the same genomic recombination of 5'-bcr and
c-abl as CML with standard Ph translocation and (b) unusual localization of
5'- bcr and c-abl sequences caused by complex Ph translocation does not
interfere with transcription of the bcr-abl fusion gene.
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