Heteromorphisms of the Philadelphia (Ph1) chromosome in patients with chronic melogenous leukaemia (CML). I. Classification and clinical significance.

In patients with chronic myelogenous leukaemia (CML), we have found the break points on the long arm of chromosome 22 (22q) are variable (heteromorphic or polymorphic). Consequently, the Philadelphia (Ph1) chromosome is heteromorphic in size for the long arm. Based upon the break points and the relative size of chromosome 22, four types of Ph1 chromosomes are proposed. They are: Types I (very large), II (large), III (average) and IV (small) with the break points at bands 22q13.3, 22q13.1, 22q12 and 22q11.3, respectively. The break points are arbitrary and should not be considered absolute since they are based on length differences. In two cases the Ph1 chromosome involved a translocation between chromosome 9 and 22, and the other two cases chromosome 1 or 12. Because Types I and II are hard to recognize by conventional techniques, the RFA technique (R. band by fluorescence with acridine orange) must be performed on all cases. An earlier contention that only chromosome 22 band 12 is concerned with abnormal myeloid cell proliferation in human leukaemia is rejected. Furthermore, break points are not restricted at the junction of 22ql and q2 and 22q2 and q3 and can happen anywhere on the long arm of chromosome 22.