The investigation of karyotypic instability in the high-hyperdiploidy subgroup of acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) of childhood has been cytogenetically we ll characterized, and approximately 25% of cases will have a high-hyperdipl oid (51-68) chromosome complement. In a 5 year period a consecutive series of 152 presentation ALL's were karyotyped. In all cases a result was obtain ed and 138 (91%) had a detectable abnormal clone of which 44 (29%) were hig h-hyperdiploid. Within the high-hyperdiploidy group karyotypic cell to cell variation was observed in many cases. To provide further evidence of this phenomenon a dual-color fluorescence in-situ hybridization (FISH) experimen t was performed on stored fixed suspension from 14 ALL's with such a karyot ype. In each case 4-6 probes were investigated, employing probes to centrom eres of chromosomes X, 4, 6, 8, and 10 and a locus specific probe to chromo some 21q22. It was found that the FISH produced results that were generally in good agreement with the G-banding findings and supported the notion of karyotypic cell to cell variation. FISH further showed that most of cases w ould have two extra copies of chromosome 21 in the majority of leukemic cel ls and a single extra copy in the minority. A further finding was that fewe r cells contained extra copies of chromosomes 6, 8 and 10 than was expected based on the comparison of the signal number of the other probes investiga ted. In contrast chromosomes X, 4, and 21 seldom displayed this feature. We have demonstrated that karyotypic instability as defined by karyotypic cel l to cell variation is a feature of the high-hyperdiploid subgroup in child hood ALL. It is questioned whether the underlying defect resulting in the o bserved karyotypic instability of this subgroup is one of the primary causa tive events in the formation of the leukemia.