Detection of trisomy 8 in Philadelphia chromosome-positive CML patients using conventional cytogenetic and interphase fluorescence in situ hybridization techniques and its relation to c-myc involvement

Trisomy 8 (+8) is a common clonal evolution marker for progression in chron ic myelogenous leukemia. The relationship of +8 to various stages of t(9;22 ) leukemias is not firmly established. To explore this association we exami ned bone marrow (BM) cells from 10 Philadelphia chromosome positive (Ph+) c hronic myeloid leukemia (CML) patients in different stages of the disease, using conventional cytogenetic technique(CCT) and interphase fluorescence i n situ hybridization (FISH). FISH detection of chromosome 8 was accomplishe d using the D8Z2 (Oncor) probe specific for the centrometric region of chro mosome 8. Five hundred interphase nuclei were counted for each patient. Thr ee of the 10 patients were selected for detection of c-myc gene locus locat ed in the 8q24.2-24.3 region using the LSI c-myc probe (Vysis). One hundred interphase nuclei were counted for the presence of the c-myc gene for each patient. We found that the percentage of interphase nuclei showing 3 hybri dization spots indicative of trisomy 8 was significantly lower by FISH than by CCT (metaphase analysis) in patients with chronic phase (CP) CML (11% v ersus 24%), nearly similar in patients with accelerated phase (AP) CML (13% versus 10%), and significantly higher in patients with myeloid blast crisi s (mBC) (81% versus 33%). Hybridization spots for the c-myc locus were cons istent with the chromosome 8 interphase FISH results in each of the patient s tested. It is hypothesized that cells with supernumerary chromosome 8 may have a cell cycle rime that differs from that of the disomic cells accordi ng to the stage of the disease. The c-myc locus expression in Ph+ CML patie nts with trisomy 8 is related to an increased copy number of the gene.