Breakpoint cluster region rearrangements in chronic myelogenous leukemia with a masked Philadelphia chromosome.

Cytogenetic and molecular analyses were performed in a case of chronic myelogenous leukemia. The cytogenetic study revealed that the leukemic cells of this patient contained a three-way translocation involving chromosomes #5, #9, and #22, resulting in a masked Philadelphia chromosome; the karyotype of the leukemic cells was 46,XY,t(5;22;9)(q31;q11;q34). Southern blot analysis of leukemic cell DNA was performed using a 1.1 kb HindIII-EcoRI breakpoint cluster region (bcr) probe. The results showed that BglII digested DNA showed two abnormal bcr fragments (i.e., 5.2 kb and 2.7 kb) in contrast to the results with DNA from two patients with a standard Ph chromosome [t(9;22)(q34;q11)] who showed one normal 5.0-kb bcr fragment in addition to altered fragments of about 4.3 kb or 4.0 kb. Bam HI digests of DNA from the leukemic cells of the patient with the masked Ph chromosome showed two bands (3.3 kb and 6.5 kb), whereas, DNA from the two patients with standard Ph translocations showed only a 3.3-kb bcr fragment. The results indicate that the molecular events in a masked Ph affect the bcr locus in a manner similar to that seen in standard Ph chromosomes.