We have sought the presence of rearrangements of the immunoglobulin he
avy chain gene locus in 13 patients with chronic myeloid leukemia (CML
) in lymphoid blastic transformation (L-BT) using the polymerase chain
reaction (PCR). The lymphoid nature of the transformation was confirm
ed by immunophenotyping and/or Southern blot hybridization with a J(H)
probe. Clonal rearrangements were detected in 85% of cases and two or
more rearrangements were visible in 64% of informative cases. The pat
tern of V-H gene family utilization revealed an apparent reduction in
V-H 4 family gene usage but otherwise reflected the known proportion o
f each gene family in the germline repertoire. In six cases the third
complementary determining regions (CDR3) of the predominant blast cris
is clone/s were sequenced revealing minimal evidence of somatic mutati
on. No clonal changes were detected in the chronic phase leukemia cell
s collected more than 6 months before the onset of L-BT in three of th
ese patients. Of the other three patients studied in chronic phase fro
m 1 to 6 months before L-BT, two showed clonal rearrangements which di
ffered in size from those present at L-BT. In one patient a V(H)3 to V
(H)5-D-H-J(H) substitution had occurred at least 3 months prior to L-B
T. In the other patient, however, the sequence of the rearrangement pr
esent 5 months prior to L-BT was unrelated to the rearrangements at th
e time of L-BT indicating a pattern of clonal succession. We conclude
that: (1) IgH gene rearrangements are detectable in the majority of pa
tients with L-BT using PCR and the lymphoid lineage of blastic CML is
most readily confirmed using consensus primers to the framework 3 regi
on; (2) somatic mutation is uncommon; and (3)B lymphoid clones distinc
t from those identified later may be detected before overt lymphoid BT
. The identification of such 'abortive' clones is evidence for clonal
instability before the onset of transformation and might have prognost
ic value.